Jun. 2025
International Academy of Toxicologic Pathology, Leadership Excellence Award
Asian Pacific Director
Dai Nakae

Aims of the Society of Preventive Medicine for Animals and Humans: Proceedings of the first annual meeting commemorating the establishment of the society　　　　　　　　　　　　　　　
Dai Nakae
Foods and Food Ingredients Journal of Japan, Apr. 2025, [Invited]

New approaches for quality of life improvement of both animals and humans　　　　　　　　　　　　　　　
Dai Nakae
Foods and Food Ingredients Journal of Japan, Apr. 2025, [Invited]

Drug review process advancement and required manufacturer and contract research oraganization responses.
Takayuki Anzai; Glenn J Myatt; Frances Hall; Brenda Finney; Kenshi Nakagawa; Hijiri Iwata; Reo Anzai; Anne Dickinson; Matthew Freer; Dai Nakae; Hiroshi Onodera; Takaaki Matsuyama
Journal of toxicologic pathology, Apr. 2024
The United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient safety. Nonetheless, society is becoming increasingly opposed to animal testing, and efforts will be made to use fewer animals and conduct fewer animal tests as a natural and reasonable response. These changes eventually alter the shape of new drug applications. Based on the assumption that fewer animal tests will be conducted or fewer animals will be used in testing, this study explored bioinformatics and new technologies as alternatives to compensate for reduced information and provide a picture of how future new drug applications may look. The authors also discuss the directions that pharmaceutical companies and nonclinical contract research organizations should adopt to promote the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibitions.

Urinary liver‐type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone‐induced acute kidney injury
Keiichi Ohata; Takeshi Sugaya; Hanh Nhung Nguyen; Karin Arai; Yuri Hatanaka; Kinuko Uno; Marika Tohma; Teppei Uechi; Keita Sekiguchi; Tsuyoshi Oikawa; Hiroshi Nagabukuro; Kanako Kuniyeda; Atsuko Kamijo‐Ikemori; Noriko Suzuki‐Kemuriyama; Dai Nakae; Eisei Noiri; Katsuhiro Miyajima
Nephrology, 11 Nov. 2023
Abstract

Aim

Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L‐FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L‐FABP increase using a more severe mouse model with histone‐induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L‐FABP as a preliminary study.

Methods

Human L‐FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L‐FABP, we used heparin and rolipram.

Results

The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L‐FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L‐FABP levels significantly decreased.

Conclusion

Histone is one of the causative agents for the increase of urinary L‐FABP at an early stage of AKI. In addition, it suggested that urinary L‐FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L‐FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test.
Motoki Hojo; Ai Maeno; Yoshimitsu Sakamoto; Yukio Yamamoto; Yuhji Taquahashi; Akihiko Hirose; Jin Suzuki; Akiko Inomata; Dai Nakae
Nanomaterials (Basel, Switzerland), 19 Jul. 2023
Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.

Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.
Keiichi Ohata; Takeshi Sugaya; Hanh Nhung Nguyen; Yuri Hatanaka; Kinuko Uno; Marika Tohma; Tsuyoshi Oikawa; Hiroshi Nagabukuro; Kanako Kuniyeda; Atsuko Kamijo-Ikemori; Noriko Suzuki-Kemuriyama; Dai Nakae; Eisei Noiri; Katsuhiro Miyajima
Nephrology (Carlton, Vic.), Jun. 2023
AIM: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases. METHODS: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.25 or 0.5 mg/kg/min calf thymus histones for 240 min from caudal vena cava. RESULTS: After the administration of histone, urinary L-FABP and gene expression of an oxidative stress marker in the kidney increased in a histone dose-dependent manner before increased serum creatinine. Upon further investigation, fibrin deposition in the glomerulus was observed and it tended to be remarkable in the high dose administrated groups. The levels of coagulation factor were significantly changed after the administration of histone, and these were significantly correlated with the levels of urinary L-FABP. CONCLUSIONS: Firstly, it was suggested that histone is one of the causative agents for the urinary L-FABP increase at an early stage of the disease with a risk of acute kidney injury. Secondly, urinary L-FABP could be a marker reflecting the changes of coagulation system and microthrombus caused by histone in the early stage of acute kidney injury before becoming severely ill and maybe a guide to early treatment initiation.

Nonalcoholic steatohepatitis-associated hepatocarcinogenesis in mice fed a modified choline-deficient, methionine-lowered, L-amino acid-defined diet and the role of signal changes.
Noriko Suzuki-Kemuriyama; Akari Abe; Sae Nakane; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
PloS one, 2023
Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and even hepatocellular carcinoma (HCC). The incidence of NASH-associated HCC is increasing, posing a serious public health threat. Unfortunately, the underlying pathological mechanisms, including the possible differences between neoplastic and non-neoplastic lesions, remain largely unknown. Previously, we reported a dietary mouse NASH model with a choline-deficient, methionine-lowered, L-amino-acid-defined, high-fat diet containing shortening without trans fatty acids (CDAA-HF-T[-]), which rapidly induces fibrosis and proliferative lesions in the liver. This study aimed to develop a mouse CDAA-HF-T(-) model capable of assessing NASH-associated hepatocarcinogenesis and identifying key signaling factors involved in its underlying mechanisms. Multiple large masses, histopathologically hepatocellular adenomas and carcinomas, and hemangiosarcomas were detected in the liver samples of mice fed CDAA-HF-T(-) for 52 or 63 weeks, along with highly advanced fibrosis and numerous foamy, phagocytic macrophages in the adjacent nontumoral area. Multiple metastatic nodules were found in the lungs of one of the animals, and lymphoid clusters were found in all CDAA-HF-T(-) group mice. In the Ingenuity Pathways Analysis of RNA expression data, the CDAA-HF-T(-) feeding revealed common signal changes in nontumoral and tumoral liver tissues, including increased IL-8 and RhoGTPases signaling and decreased lipid metabolism. Meanwhile, macrophage inflammatory protein 2 (MIP-2) expression levels were upregulated in nontumoral liver tissue from the end of Week 13 of CDAA-HF-T(-) feeding to the end of Week 63. On the other hand, MIP-2 was expressed on macrophages in non-tumor areas and hepatocytes in tumor areas. Therefore, the CDAA-HF-T(-) mouse model is useful for assessing NASH and NASH-associated hepatocarcinogenesis, and IL-8 signaling plays important roles in NASH-associated carcinogenesis and cirrhosis, but it may also play different roles in nontumoral liver tissue and tumorigenesis.

Continuous infiltration of small peritoneal macrophages in the mouse peritoneum through CCR2-dependent and -independent routes during fibrosis and mesothelioma development induced by a multiwalled carbon nanotube, MWNT-7.
Motomu Shimizu; Motoki Hojo; Kiyomi Ikushima; Yukio Yamamoto; Ai Maeno; Yoshimitsu Sakamoto; Naozumi Ishimaru; Yuhji Taquahashi; Jun Kanno; Akihiko Hirose; Jin Suzuki; Akiko Inomata; Dai Nakae
The Journal of toxicological sciences, 2023
Although toxicities of multiwalled carbon nanotube (MWCNT) have been found to be related with activities of macrophages phagocytosing the fibers, the exact relationship between macrophage population and pathogenesis of fibrosis and mesotheliomas induced by MWCNTs is largely unknown. CCL2-CCR2 axis, a major monocyte/macrophage infiltration route, is thought to be involved in not only acute inflammation but also the formation of tumor microenvironment. We therefore described a time-course of alteration of macrophage population in an attempt to clarify the contribution of the Ccr2 gene to mesotheliomagenesis. Wild-type (WT) C57BL/6 mice and Ccr2-knockout (KO) mice were intraperitoneally administered with MWNT-7 and were sequentially necropsied at 1, 7, 28, 90, and 245 day(s) after the injection. Peritoneal fibrosis was prominent in all MWCNT-treated mice, with a lower severity in the KO mice. No differences were observed in the incidences of neoplastic lesions of mesothelia between WT and KO mice. A flow cytometric analysis revealed that after gross disappearance of macrophages after MWCNT exposure, small peritoneal macrophages (SPMs) were exclusively refurbished by the CCR2-dependent route at day 1 (as Ly-6C+MHC class II- cells), followed by additional CCR2-independent routes (as Ly-6C-MHC class II- cells); i.e., the only route in KO mice; with a delay of 1-7 days. The SPMs derived from both routes appeared to differentiate into maturated cells as Ly-6C-MHC class II+, whose ratio increased in a time-dependent manner among the total SPM population. Additionally, most macrophages expressed M1-like features, but a small fraction of macrophages exhibited an M1/M2 mixed status in MWCNT-treated animals. Our findings demonstrate a long-persistent activation of the CCL2-CCR2 axis after MWCNT exposure and enable a better understanding of the participation and potential roles of SPMs in fibrous material-induced chronic toxicities.

Effects of Siraitia grosvenorii extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet
Kinuko Uno; Katsuhiro Miyajima; Shuji Ogawa; Noriko Suzuki-Kemuriyama; Dai Nakae
Journal of Toxicologic Pathology, 2023

Effects of Siraitia grosvenorii extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet
Kinuko Uno; Katsuhiro Miyajima; Shuji Ogawa; Noriko Suzuki-Kemuriyama; Dai Nakae
JOURNAL OF TOXICOLOGIC PATHOLOGY, 2023

Effects of Siraitia grosvenorii extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet.
Kinuko Uno; Katsuhiro Miyajima; Shuji Ogawa; Noriko Suzuki-Kemuriyama; Dai Nakae
Journal of toxicologic pathology, Jan. 2023
Siraitia grosvenorii is the fruit of a cucurbitaceous vine endemic to China. Its extract has been used as a sweetener and exhibits various anti-inflammatory and anticarcinogenic effects mediated via its antioxidant properties. In the present study, we aimed to clarify the preventive or ameliorative effects of S. grosvenorii extract (SGE) on nonalcoholic steatohepatitis-like lesions induced in male Hsd: Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet for 13 weeks. This diet increased hepatotoxicity parameters and upregulated the expression of inflammation- and fibrosis-related genes in the liver, resulting in the progression of hepatic lesions, oxidative stress, hepatocellular apoptosis, and fibrosis. Furthermore, this diet upregulated the expression of phosphorylated nuclear factor-κB (NF-κB) and CD44. SGE administration inhibited these lesions, similar to CD44, a factor that controls hepatic inflammation and fibrosis. These results revealed that SGE impacts the disease stage via antioxidative effects and regulation of CD44 expression. SGE was found to be useful for preventing and treating steatohepatitis.

Correction to: A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a cholinedeficient, methionine-lowered, L-amino acid-defined, high-fat diet. (Lipids in Health and Disease, (2020), 19, 1, (251), 10.1186/s12944-020-01423-3)
Noriko Suzuki-Kemuriyama; Akari Abe; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
Lipids in Health and Disease, Dec. 2022

Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats
Motoki Hojo; Ai Maeno; Yoshimitsu Sakamoto; Aya Ohnuki; Yukie Tada; Yukio Yamamoto; Kiyomi Ikushima; Ryota Inaba; Jin Suzuki; Yuhji Taquahashi; Satoshi Yokota; Norihiro Kobayashi; Makoto Ohnishi; Yuko Goto; Takamasa Numano; Hiroyuki Tsuda; David B. Alexander; Jun Kanno; Akihiko Hirose; Akiko Inomata; Dai Nakae
Particle and Fibre Toxicology, Dec. 2022
Abstract

Background

A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study.

Results

Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent.

Conclusions

Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.

CD44 expression in the bile duct epithelium is related to hepatic fibrosis in nonalcoholic steatohepatitis rats induced by a choline-deficient, methionine-lowered, L-amino acid diet.
Kinuko Uno; Katsuhiro Miyajima; Marika Toma; Noriko Suzuki-Kemuriyama; Dai Nakae
Journal of toxicologic pathology, Apr. 2022
Nonalcoholic steatohepatitis is a lifestyle-related disease and an increasing threat worldwide. Hepatic fibrosis, which results from chronic hepatic diseases including nonalcoholic steatohepatitis, is closely correlated with mortality among hepatic lesions, such as steatosis and inflammation. Thus, it is important to identify factors that can serve as diagnostic and therapeutic targets for hepatic fibrosis. In this study, we examined the function of CD44 in the development of hepatic fibrosis in choline-deficient, methionine-lowered, L-amino-acid diet-fed rats, especially with respect to the proliferation of bile duct epithelium. Male Fischer 344 rats were fed a choline-deficient, methionine-lowered, L-amino-acid diet for 2, 4, 13, or 26 weeks. This diet decreased the body weight; increased the levels of serum parameters indicating liver injury, such as aspartate and alanine aminotransferase; upregulated inflammation- and fibrosis-related gene expression in the liver; and resulted in the development of hepatic lesions, including fatty changes in hepatocytes, inflammatory cell infiltration, and fibrosis. Hepatic hyaluronan was synthesized and deposited in the liver tissue. The expression of both CD44 mRNA and protein was significantly increased throughout the experimental period. CD44 protein was observed in some of the bile duct epithelium, around which hyaluronic acid was deposited, and these bile duct lesions were concordant with the area of hepatic fibrosis. Thus, CD44 expressed in the bile duct epithelium may be a target for controlling nonalcoholic steatohepatitis-related hepatic fibrosis.

Iron oxide nanoparticles exert inhibitory effects on N-Bis(2-hydroxypropyl)nitrosamine (DHPN)-induced lung tumorigenesis in rats.
Yukie Tada; Motoki Hojo; Katsuhiro Yuzawa; Akemichi Nagasawa; Jin Suzuki; Akiko Inomata; Takako Moriyasu; Dai Nakae
Regulatory toxicology and pharmacology : RTP, Feb. 2022
Iron oxide nanoparticles (magnetite) have been widely used in industry and medicine. However, the safety assessment of magnetite has not been fully completed. The present study was conducted to assess effects of magnetite on carcinogenic activity, using a medium-term bioassay protocol. A total of 100 male Fischer 344 rats, 6 weeks old, were randomly divided into 5 groups of 20 animals each, and given a basal diet and drinking water containing 0 or 0.1% of N-bis(2-hydroxypropyl)nitrosamine (DHPN) for 2 weeks. Two weeks later, the rats were intratracheally instilled magnetite 7 times at an interval of 4 weeks, at the doses of 0, 1.0 or 5.0 mg/kg body weight, and sacrificed at the end of the experimental period of 30 weeks. The multiplicities of macroscopic lung nodules and histopathologically diagnosed bronchiolo-alveolar hyperplasia, induced by DHPN, were both significantly decreased by the high dose of magnetite. The expression of minichromosome maintenance (MCM) protein 7 in non-tumoral alveolar epithelial cells, and the number of CD163-positive macrophages in tumor nodules were both significantly reduced by magnetite. It is suggested that magnetite exerts inhibitory effects against DHPN-induced lung tumorigenesis, by the reduction of alveolar epithelial proliferation and the M2 polarization of tumor-associated macrophages.

Correction to: A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a cholinedeficient, methionine-lowered, L-amino acid-defined, high-fat diet.
Noriko Suzuki-Kemuriyama; Akari Abe; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
Lipids in health and disease, 07 Jan. 2022

CD44 expression in the bile duct epithelium is related to hepatic fibrosis in nonalcoholic steatohepatitis rats induced by a choline-deficient, methionine-lowered, L-amino acid diet
Kinuko Uno; Katsuhiro Miyajima; Marika Toma; Noriko Suzuki Kemuriyama; Dai Nakae
Journal of Toxicologic Pathology, 2022

CD44 expression in the bile duct epithelium is related to hepatic fibrosis in nonalcoholic steatohepatitis rats induced by a choline-deficient, methionine-lowered, L-amino acid diet
Kinuko Uno; Katsuhiro Miyajima; Marika Toma; Noriko Suzuki-Kemuriyama; Dai Nakae
JOURNAL OF TOXICOLOGIC PATHOLOGY, 2022

Nonobese mice with nonalcoholic steatohepatitis fed on a choline-deficient, l-amino acid-defined, high-fat diet exhibit alterations in signaling pathways
Noriko Suzuki-Kemuriyama; Akari Abe; Sae Nakane; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
FEBS Open Bio, Nov. 2021

Nonobese mice with nonalcoholic steatohepatitis fed on a choline-deficient, l-amino acid-defined, high-fat diet exhibit alterations in signaling pathways
Noriko Suzuki-Kemuriyama; Akari Abe; Sae Nakane; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
FEBS OPEN BIO, Nov. 2021

Nonobese mice with nonalcoholic steatohepatitis fed on a choline-deficient, l-amino acid-defined, high-fat diet exhibit alterations in signaling pathways.
Noriko Suzuki-Kemuriyama; Akari Abe; Sae Nakane; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
FEBS open bio, Nov. 2021
Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline-deficient, methionine-lowered, l-amino acid-defined high-fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors/pathways detected in this study may assist in future study of NASH regulation, especially its 'nonobese' subtype.

A case of spontaneous zymbal’s gland carcinoma with lung metastasis in an aged fischer 344 rat
Ai Maeno; Yoshimitsu Sakamoto; Motoki Hojo; Yukie Tada; Jin Suzuki; Akiko Inomata; Takako Moriyasu; Akihiko Hirose; Noriko Kemuriyama; Katsuhiro Miyajima; Dai Nakae
Journal of Toxicologic Pathology, 01 Oct. 2021

Histological sequence of the development of rat mesothelioma by MWCNT, with the involvement of apolipoproteins.
Motoki Hojo; Yukio Yamamoto; Yoshimitsu Sakamoto; Ai Maeno; Aya Ohnuki; Jin Suzuki; Akiko Inomata; Takako Moriyasu; Yuhji Taquahashi; Jun Kanno; Akihiko Hirose; Dai Nakae
Cancer science, 04 Mar. 2021
A rat model of mesothelioma development by peritoneal injection of multiwalled carbon nanotube (MWCNT) has been established and found to be useful to understand the mechanisms underlying fibrous particles-associated carcinogenesis. Its detailed histological sequence, however, remains largely obscure. We therefore aimed to assess the time-course of mesothelioma development by MWCNT and evaluate a set of lipoprotein-related molecules as potential mechanism-based biomarkers for the phenomenon. Male Fischer 344 rats were injected intraperitoneally (ip) with MWCNT (MWNT-7) at 1 mg/kg body weight, and necropsied at 8, 16, 24, 32, or 42 wk after injection. For biochemical analyses of the lipoprotein-related molecules, more samples, including severe mesothelioma cases, were obtained from 2 other carcinogenicity tests. Histologically, in association with chronic inflammation, mesothelial proliferative lesions appeared at c. Wk-24. Before and at the beginning of the tumor development, a prominent infiltration of CD163-positive cells was seen near mesothelial cells. The histological pattern of early mesothelioma was not a papillary structure, but was a characteristic structure with a spherical appearance, composed of the mesothelioma cells in the surface area that were underlain by connective tissue-like cells. Along with the progression, mesotheliomas started to show versatile histological subtypes. Serum levels of apolipoprotein A-I and A-IV, and a ratio of HDL cholesterol to total cholesterol were inversely correlated with mesothelioma severity. Overall, the detailed histological sequence of mesotheliomagenesis by MWCNT is demonstrated, and indicated that the altered profile of apolipoproteins may be involved in its underlying mechanisms.

Glomerular Hyperfiltration With Hyperglycemia in the Spontaneously Diabetic Torii (SDT) Fatty Rat, an Obese Type 2 Diabetic Model
Ryuhei Sano; Yukihito Ishii; Masao Yamanaka; Yuzo Yasui; Yusuke Kemmochi; Fuko Kuroki; Miki Sugimoto; Sumiaki Fukuda; Tomohiko Sasase; Katsuhiro Miyajima; Dai Nakae; Takeshi Ohta
Physiological Research, Feb. 2021

Effects of excessive sodium chloride loading in the spontaneously diabetic torii (Sdt) fatty rats, a preclinical model of type 2 diabetes mellitus
Soon Hui Teoh; Katsuhiro Miyajima; Yuichi Shinozaki; Masami Shinohara; Keiichi Ohata; François Briand; Rika Morimoto; Yuka Nakamura; Kinuko Uno; Noriko Kemuriyama; Dai Nakae; Takeshi Ohta; Tatsuya Maekawa
Journal of Toxicological Sciences, 2021

Effects of excessive sodium chloride loading in the spontaneously diabetic torii (SDT) fatty rats, a preclinical model of type 2 diabetes mellitus
Soon Hui Teoh; Katsuhiro Miyajima; Yuichi Shinozaki; Masami Shinohara; Keiichi Ohata; Francois Briand; Rika Morimoto; Yuka Nakamura; Kinuko Uno; Noriko Kemuriyama; Dai Nakae; Takeshi Ohta; Tatsuya Maekawa
JOURNAL OF TOXICOLOGICAL SCIENCES, 2021

Effects of excessive sodium chloride loading in the spontaneously diabetic torii (SDT) fatty rats, a preclinical model of type 2 diabetes mellitus.
Soon Hui Teoh; Katsuhiro Miyajima; Yuichi Shinozaki; Masami Shinohara; Keiichi Ohata; François Briand; Rika Morimoto; Yuka Nakamura; Kinuko Uno; Noriko Kemuriyama; Dai Nakae; Takeshi Ohta; Tatsuya Maekawa
The Journal of toxicological sciences, 2021
Type 2 diabetes mellitus represents an international health concern with its growing number of patients worldwide. At the same time, excessive salt consumption is also seen as a major cause of diseases such as hypertension and may expedite renal complications in diabetic patients. In this study, we investigated the effects of excessive sodium chloride supplementation on the kidney of the Spontaneously Diabetic Torii-Leprfa (SDT fatty) rat, an obese type 2 diabetes model. Male and female SDT fatty rats and normal Sprague-Dawley (SD) rats at 5 weeks of age were loaded with 0.3% sodium chloride (NaCl) in drinking water for 13 weeks. Blood serum and urinary parameters were observed throughout the experiment and kidney samples were examined in histopathological and genetical analyses. Significant changes on the body weight, blood pressure, urine volume, creatinine clearance, blood urea nitrogen (BUN), relative gene expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-β (TGF-β) were observed in the salt-loaded male SDT fatty rats. Urinary L-type fatty acid-binding protein (L-FABP) and albumin levels were higher observed in the salt-loaded male SDT fatty rats throughout the period, but urinary albumin levels in the female SDT fatty rats remain unchanged. In the kidney, slight Armani-Ebstein changes, tubular degeneration, hyaline cast, and inflammatory cell infiltration were observed in female SDT fatty rats while the levels of some changes were higher in the salt-loaded group. The kidney of the salt-loaded male SDT fatty rats demonstrated a higher degree of lesions compared to the female group and the male unloaded group. Histopathological changes in salt-loaded SDT fatty rats show that excessive salt consumption may act as a diabetic pathology exacerbation factor, but the pathology may be influenced by gender difference. Urinary L-FABP levels may act as a useful biomarker to detect slight tubular damages in the kidney. Excessive salt loading was shown to exacerbate the renal injury in SDT fatty rats.

A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet.
Noriko Suzuki-Kemuriyama; Akari Abe; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
Lipids in health and disease, 14 Dec. 2020
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease characterized by steatosis, necroinflammation, and fibrosis, resulting in cirrhosis and cancer. Efforts have focused on reducing the intake of trans fatty acids (TFAs) because of potential hazards to human health and the increased risk for NASH. However, the health benefits of reducing dietary TFAs have not been fully elucidated. Here, the effects of TFAs vs. a substitute on NASH induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet (CDAA-HF) were investigated. METHODS: Mice were fed CDAA-HF containing shortening with TFAs (CDAA-HF-T(+)), CDAA-HF containing shortening without TFAs (CDAA-HF-T(-)), or a control chow for 13 or 26 weeks. RESULTS: At week 13, NASH was induced in mice by feeding CDAA-HF-T(+) containing TFAs or CDAA-HF-T(-) containing no TFAs, but rather mostly saturated fatty acids (FAs), as evidenced by elevated serum transaminase activity and liver changes, including steatosis, inflammation, and fibrosis. CDAA-HF-T(-) induced a greater extent of hepatocellular apoptosis at week 13. At week 26, proliferative (preneoplastic and non-neoplastic) nodular lesions were more pronounced in mice fed CDAA-HF-T(-) than CDAA-HF-T(+). CONCLUSIONS: Replacement of dietary TFAs with a substitute promoted the development of proliferation lesions in the liver of a mouse NASH model, at least under the present conditions. Attention should be paid regarding use of TFA substitutes in foods for human consumption, and a balance of FAs is likely more important than the particular types of FAs.

A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet
Noriko Suzuki-Kemuriyama; Akari Abe; Kiniko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
Lipids in Health and Disease, Dec. 2020

A Trans Fatty Acid Substitute Aggravates Nonalcoholic Steatohepatitis Induced in Mice by Feeding a Choline-Deficient, Methionine-Lowered, L-Amino Acid-Defined, High-Fat Diet
Noriko Suzuki-Kemuriyama; Akari Abe; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
21 Sep. 2020

Identification of descarbonsildenafil in an adulterated dietary supplement and evaluation of its inhibitory activity for phosphodiesterase type 5 (PDE5)
Yoko Ichikawa-Kaji; Junichi Nakajima; Shoko Kikkawa; Fujio Ishizawa; Rei Nishiyama; Kiyoko Kishimoto; Nozomi Uemura; Miki Satoh; Jin Suzuki; Akiko Inomata; Dai Nakae; Isao Azumaya; Katsuya Honda; Takako Moriyasu
Journal of the Food Hygienic Society of Japan, Feb. 2020

Impact of altered dietary calcium–phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries
Atsushi Watanabe; Toshinori Koizumi; Takumi Horikawa; Yusuke Sano; Haruka Uki; Katsuhiro Miyajima; Noriko Kemuriyama; Reo Anzai; Hijiri Iwata; Takayuki Anzai; Kenshi Nakagawa; Dai Nakae
Journal of Toxicologic Pathology, 2020

A histopathological analysis of spontaneous neoplastic and non-neoplastic lesions in aged male RccHan:WIST rats
Motoki Hojo; Yoshimitsu Sakamoto; Ai Maeno; Kuniaki Tayama; Yukie Tada; Katsuhiro Yuzawa; Hiroshi Ando; Yoshikazu Kubo; Akemichi Nagasawa; Kazuyoshi Tanaka; Norio Yano; Fujifumi Kaihoko; Yuko Hasegawa; Toshinari Suzuki; Akiko Inomata; Takako Moriyasu; Katsuhiro Miyajima; Dai Nakae
Journal of Toxicologic Pathology, 2020

Establishment of the Global SEND Alliance (G-SEND) in Japan and efficient creation of electronic SEND datasets between CROs.
Takayuki Anzai; Takaaki Matsuyama; Michael Wasko; Hirofumi Hatakeyama; Shin-Ichi Horikawa; Reo Anzai; Hijiri Iwata; Norio Imai; Fukutaro Mizuhashi; Masaru Tsuboi; Takeshi Okuzono; Hisayoshi Takagi; Hyeon Cho; Bryan Tan Siang Rong; Fumio Masaki; Dai Nakae
Journal of toxicologic pathology, Apr. 2019
The Standard for Exchange of Nonclinical Data (SEND), adopted by the US Food and Drug Administration (FDA), is a set of regulations for digitalization and standardization of nonclinical study data; thus, related organizations have begun implementing processes in support of SEND. The Global Editorial and Steering Committee (GESC), which provides oversight of the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND), has prepared the SEND Controlled Terminology (CT) for toxicologic pathology. SEND provides electronic data standards created by the Clinical Data Interchange Standards Consortium (CDISC), and CDISC also collaborates in the implementation of SEND. Furthermore, the Pharmaceutical Users Software Exchange (PhUSE), which includes members of the US FDA, has conducted various activities to promote realistic and effective methods to implement SEND. As we reported in 2015, there is a significant variation in the efficiency and quality of SEND data implementation across pharmaceutical companies and contractors (CROs) globally. To address this problem, the Global SEND Alliance (G-SEND) was established in August 2018 to facilitate the coordination and standardization of SEND datasets across CROs in Asia. This paper reports the first method for organizationally and jointly creating consistent SEND datasets between CROs using G-SEND.

Hepatic lesions induced by feeding Western diets to Zucker fatty rats, an insulin-resistant model.
Tomoyuki Saito; Yasufumi Toriniwa; Yukihito Ishii; Atsuhiro Uemura; Katsuhiro Miyajima; Kinuko Uno; Yuki Shirai; Dai Nakae; Takeshi Ohta
Journal of toxicologic pathology, Oct. 2018
Metabolic diseases including nonalcoholic steatohepatitis develop due to various environmental factors. In particular, the westernization of food is closely related to the development of these diseases. In this study, we investigated pathophysiological changes in the livers of Zucker fatty (ZF) rats induced by feeding Western diets. Male ZF rats were fed a sucrose/fat/cholesterol-enriched diet (Western diet, WD) or standard diet (SD) for 18 weeks, from 7 to 25 weeks of age. Body weight, food intake, and biochemical parameters were periodically measured, histopathological analyses were performed at 25 weeks, and mRNA expression in the liver was determined. ZF rats fed the WD (ZF-WD rats) developed obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia, and their alanine aminotransferase and aspartate aminotransferase levels increased compared with those of ZF rats fed the SD (ZF-SD rats). Hepatic lesions including fibrosis and necrosis were observed in the ZF-WD rats at 25 weeks; however, fibrosis and necrosis were not observed in the ZF-SD rats. Oxidative stress markers also increased in the livers of ZF-WD rats. Hepatic mRNA expression related to inflammation and fibrosis increased in the ZF-WD rats; however, mRNA expression related to lipid synthesis decreased. Microsomal triglyceride transfer protein mRNA levels in the ZF-WD rats also decreased. In Zucker lean rats fed the WD, similar changes were observed in the liver; however, the hepatic changes were not serious compared with ZF-WD rats. In conclusion, hepatic lesions, such as inflammation, fibrosis, and necrosis, were observed in the ZF-WD rats. The sucrose/fat/cholesterol-enriched diet induced significant lipotoxicity in the livers of animals in this insulin-resistant model.

Establishment of an in vivo simulating co-culture assay platform for genotoxicity of multi-walled carbon nanotubes
Emi Fukai; Haruna Sato; Masatoshi Watanabe; Dai Nakae; Yukari Totsuka
Cancer Science, 01 Apr. 2018, [Reviewed]

Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes with different physicochemical characteristics by a single intraperitoneal injection in male Fischer 344 rats
Yoshimitsu Sakamoto; Motoki Hojo; Yuki Kosugi; Kimiyo Watanabe; Akihiko Hirose; Akiko Inomata; Toshinari Suzuki; Dai Nakae
Journal of Toxicological Sciences, 2018

Effect of dosing frequency of teriparatide (PTH 1-34) on bone formation in rats: Comparison of bone metabolism marker levels
Atsushi Watanabe; Kazuyuki Tsurui; Shigeki Yoneyama; Hijiri Iwata; Takayuki Anzai; Christopher Jerome; Dai Nakae
Journal of Toxicological Sciences, 2018

Hepatic lesions induced by feeding western diets to Zucker fatty rats, an insulin-resistant model
Tomoyuki Saito; Yasufumi Toriniwa; Yukihito Ishii; Atsuhiro Uemura; Katsuhiro Miyajima; Kinuko Uno; Yuki Shirai; Dai Nakae; Takeshi Ohta
Journal of Toxicologic Pathology, 2018

Hepatic lesions induced by feeding Western diets to Zucker fatty rats, an insulin-resistant model
Tomoyuki Saito; Yasufumi Toriniwa; Yukihito Ishii; Atsuhiro Uemura; Katsuhiro Miyajima; Kinuko Uno; Yuki Shirai; Dai Nakae; Takeshi Ohta
JOURNAL OF TOXICOLOGIC PATHOLOGY, 2018

Absence of in vivo mutagenicity of multiwalled carbon nanotubes in single intratracheal instillation study using F344 gpt delta rats
Katsuyoshi Horibata; Akiko Ukai; Akio Ogata; Dai Nakae; Hiroshi Ando; Yoshikazu Kubo; Akemichi Nagasawa; Katsuhiro Yuzawa; Masamitsu Honma
Genes and Environment, 2017, [Reviewed]

Specific pathologist responses for standard for exchange of nonclinical data (SEND)
Atsushi Watanabe; Osamu Kusuoka; Norihiro Sato; Osamu Nakazono; Michael Wasko; Daniel Potenta; Dai Nakae; Hirofumi Hatakeyama; Hijiri Iwata; Misaki Naota; Takayuki Anzai
Journal of Toxicologic Pathology, 2017, [Reviewed]

Extracts of black and brown rice powders improve hepatic lipid accumulation via the activation of PPAR alpha in obese and diabetic model mice
Angelina D. R. Felix; Nobuyuki Takahashi; Mami Takahashi; Rie Katsumata-Tsuboi; Ryo Satoh; Teoh Soon Hui; Katsuhiro Miyajima; Dai Nakae; Hirofumi Inoue; Mariko Uehara
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2017, [Reviewed]

Identification of (1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (DP-UR-144) in a herbal drug product that was commercially available in the Tokyo metropolitan area
Yoko Ichikawa; Jun'ichi Nakajima; Misako Takahashi; Nozomi Uemura; Masao Yoshida; Atsuko Suzuki; Jin Suzuki; Dai Nakae; Takako Moriyasu; Mitsugu Hosaka
FORENSIC TOXICOLOGY, Jan. 2017, [Reviewed]

Effects Induced by Organic Acids in a Human Lung Alveolar Carcinoma Cell Line A549
Tomoko Okubo; Toshinari Suzuki; Mitsugu Hosaka; Dai Nakae
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, Oct. 2016, [Reviewed]

Different effects of eicosapentaenoic and docosahexaenoic acids on atherogenic high- fat diet-induced non-alcoholic fatty liver disease in mice
Suzuki-Kemuriyama Noriko; Takashi Matsuzaka; Motoko Kuba; Hiroshi Ohno; Songiee Han; Yoshinori Takeuchi; Masaaki Isaka; Kazuto Kobayashi; Hitoshi Iwasaki; Shigeru Yatoh; Hiroaki Suzuki; Katsuhiro Miyajima; Dai Nakae; Naoya Yahagi; Yoshimi Nakagawa; Hirohito Sone; Nobuhiro Yamada; Hitoshi Shimano
PLoS ONE, 01 Jun. 2016, [Reviewed]

Time course of carcinogenesis by MWCNT in rats
HOJO Motoki; SAKAMOTO Yoshimitsu; FUJITANI Tomoko; YAMAMOTO Yukio; HASEGAWA Yuko; TADA Yukie; KUBO Yoshikazu; NAGASAWA Akemichi; KAIHOKO Fujifumi; TAKAHASHI Hiroshi; YUZAWA Katsuhiro; ANDO Hiroshi; TANAKA Kazuyoshi; HIROSE Akihiko; INOMATA Akiko; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2016

Comparative effects of sulfhydryl compounds on target organellae, nuclei and mitochondria, of hydroxylated fullerene-induced cytotoxicity in isolated rat hepatocytes
Yoshio Nakagawa; Akiko Inomata; Akio Ogata; Dai Nakae
JOURNAL OF APPLIED TOXICOLOGY, Dec. 2015, [Reviewed]

Expression of MAS1 in breast cancer.
Yi Luo; Eriko Tanabe; Misaho Kitayoshi; Yukiko Nishiguchi; Rina Fujiwara; Sayako Matsushima; Takamitsu Sasaki; Tomonori Sasahira; Yoshitomo Chihara; Dai Nakae; Kiyomu Fujii; Hitoshi Ohmori; Hiroki Kuniyasu
Cancer science, Sep. 2015
MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. MAS1 induces anti-A-II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast. While benign mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDC, especially in scirrhous IDC. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS1. Using the TNBC cell lines 4T1 and MDA-MB-468, which expresses MAS1, we found that cell growth, anti-apoptotic survival and invasion were suppressed by MAS1 activation with A1-7 treatment and enhanced by MAS1 knockdown. In contrast, synergic effect was found between tamoxifen and A1-7 in a luminal A breast cancer cell line, MCF-7. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.

Chemokine (C‐C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient‐based study
Jiegou Xu; David B. Alexander; Masaaki Iigo; Hirokazu Hamano; Satoru Takahashi; Takako Yokoyama; Munehiro Kato; Ikuji Usami; Takeshi Tokuyama; Masahiro Tsutsumi; Mouka Tamura; Tetsuya Oguri; Akio Niimi; Yoshimitsu Hayashi; Yoshifumi Yokoyama; Ken Tonegawa; Katsumi Fukamachi; Mitsuru Futakuchi; Yuto Sakai; Masumi Suzui; Michihiro Kamijima; Naomi Hisanaga; Toyonori Omori; Dai Nakae; Akihiko Hirose; Jun Kanno; Hiroyuki Tsuda
Cancer Science, Jul. 2015, [Reviewed]

In vitro effects induced by diesel exhaust at an air-liquid interface in a human lung alveolar carcinoma cell line A549
Tomoko Okubo; Mitsugu Hosaka; Dai Nakae
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, Jul. 2015, [Reviewed]

Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study
Jiegou Xu; David B. Alexander; Masaaki Iigo; Hirokazu Hamano; Satoru Takahashi; Takako Yokoyama; Munehiro Kato; Ikuji Usami; Takeshi Tokuyama; Masahiro Tsutsumi; Mouka Tamura; Tetsuya Oguri; Akio Niimi; Yoshimitsu Hayashi; Yoshifumi Yokoyama; Ken Tonegawa; Katsumi Fukamachi; Mitsuru Futakuchi; Yuto Sakai; Masumi Suzui; Michihiro Kamijima; Naomi Hisanaga; Toyonori Omori; Dai Nakae; Akihiko Hirose; Jun Kanno; Hiroyuki Tsuda
Cancer Science, 01 Jul. 2015, [Reviewed]

Effects of phenyl N-tert-butyl nitrone (PBN) on induction of mesothelial and pulmonary proliferative lesions by multi-wall carbon nanotube (CNT) in rats
SAKAMOTO Yoshimitsu; OGATA Akio; HOJO Motoki; YUZAWA Katsuhiro; ANDO Hiroshi; KUBO Yoshikazu; NAGASAWA Akemichi; TAKAHASHI Hiroshi; HIROSE Akihiko; INOUE Yoshiyuki; HASHIZUME Naoki; INOMATA Akiko; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2015

Spontaneous neoplastic and non-neoplastic lesions in aging male RccHan:WIST rats
HOJO Motoki; SAKAMOTO Yoshimitsu; TADA Yukie; OGATA Akio; YUZAWA Katsuhiro; ANDO Hiroshi; KUBO Yoshikazu; NAGASAWA Akemichi; KAIHOKO Fujifumi; TAKAHASHI Hiroshi; YANO Norio; INOMATA Akiko; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2015

Coparison of fetal toxicity of various multi-wall carbon nanotubes in mice
FUJITANI Tomoko; INOMATA Akiko; OGATA Akio; ANDO Hiroshi; KUBO Yoshikazu; NAKAE Dai; HIROSE Akihiko; NISHIMURA Tetsuji; IKEDA Reiko
Annual Meeting of the Japanese Society of Toxicology, 2015

Effects of maternal piperonyl butoxide exposure on behavioral development in F₁-generation mice
TANAKA Toyohito; OGATA Akio; INOMATA Akiko; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2015

Comparison of fetal toxicity of various multi-wall carbon nanotubes in mice
Tomoko Fujitani; Akiko Inomata; Akio Ogata; Yoshimitsu Sakamoto; Akihiko Hirose; Tetsuji Nishimura; Reiko Ikeda; Dai Nakae
Toxicology Reports, 2015, [Reviewed]

Identification of N,N-bis(1-pentylindol-3-yl-carboxy)naphthylamine (BiPICANA) found in an herbal blend product in the Tokyo metropolitan area and its cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays
Jun’ichi Nakajima; Misako Takahashi; Nozomi Uemura; Takako Seto; Haruhiko Fukaya; Jin Suzuki; Masao Yoshida; Maiko Kusano; Hiroshi Nakayama; Kei Zaitsu; Akira Ishii; Takako Moriyasu; Dai Nakae
Forensic Toxicology, 2015, [Reviewed]

OCCURRENCE AND BEHAVIOR OF THE CHIRAL ANTI-INFLAMMATORY DRUG NAPROXEN IN AN AQUATIC ENVIRONMENT
Toshinari Suzuki; Yuki Kosugi; Mitsugu Hosaka; Tetsuji Nishimura; Dai Nakae
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, Dec. 2014, [Reviewed]

Rapid identification of a narcotic plant Papaver bracteatum using flow cytometry
Masako Aragane; Daisuke Watanabe; Jun'ichi Nakajima; Masao Yoshida; Masao Yoshizawa; Tomohiro Abe; Rei Nishiyama; Jin Suzuki; Takako Moriyasu; Dai Nakae; Hiroshi Sudo; Hiroyuki Sato; Atuyuki Hishida; Nobuo Kawahara; So Makabe; Ikuo Nakamura; Masahiro Mii
JOURNAL OF NATURAL MEDICINES, Oct. 2014, [Reviewed]

Effects of Different Types of Bedding Materials on Behavioral Development in Laboratory CD1 Mice (Mus musculus)
Toyohito Tanaka; Akio Ogata; Akiko Inomata; Dai Nakae
BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, Oct. 2014, [Reviewed]

High-temperature calcined fullerene nanowhiskers as well as long needle-like multi-wall carbon nanotubes have abilities to induce NLRP3-mediated IL-1 beta secretion
Hongyan Cui; Weijia Wu; Keiichiro Okuhira; Kun'ichi Miyazawa; Takayuki Hattori; Kimie Sai; Mikihiko Naito; Kazuhiro Suzuki; Tetsuji Nishimura; Yoshimitsu Sakamoto; Akio Ogata; Tomokazu Maeno; Akiko Inomata; Dai Nakae; Akihiko Hirose; Tomoko Nishimaki-Mogami
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Sep. 2014, [Reviewed]

Teratogenicity of asbestos in mice
Tomoko Fujitani; Motoki Hojo; Akiko Inomata; Akio Ogata; Akihiko Hirose; Tetsuji Nishimura; Dai Nakae
JOURNAL OF TOXICOLOGICAL SCIENCES, Apr. 2014, [Reviewed]

Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response.
Totsuka Y; Ishino K; Kato T; Goto S; Tada Y; Nakae D; Watanabe M; Wakabayashi K
Nanomaterials (Basel, Switzerland), Mar. 2014, [Reviewed]
Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

Multi-step lung carcinogenesis model induced by oral administration of N-nitrosobis(2-hydroxypropyl)amine in rats
Toshifumi Tsujiuchi; Dai Nakae; Yoichi Konishi
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, Mar. 2014, [Reviewed]

Effects of different bedding materials on behavioral development in F1-generation mice
TANAKA Toyohito; OGATA Akio; INOMATA Akiko; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2014

Pancreatic ductal adenocarcinoma in a Wistar Hannover GALAS rat
Yusuke Kuroda; Seigo Hayashi; Soichiro Hagio; Masayoshi Abe; Satoshi Furukawa; Dai Nakae
Journal of Toxicologic Pathology, 2014, [Reviewed]

Identification of a synthetic cannabinoid A-836339 as a novel compound found in a product
Nozomi Uemura; Haruhiko Fukaya; Chieko Kanai; Masao Yoshida; Jun'ichi Nakajima; Misako Takahashi; Jin Suzuki; Takako Moriyasu; Dai Nakae
FORENSIC TOXICOLOGY, Jan. 2014, [Reviewed]

Effects of N-acetyl-l-cysteine on target sites of hydroxylated fullerene-induced cytotoxicity in isolated rat hepatocytes
Yoshio Nakagawa; Toshinari Suzuki; Kazuo Nakajima; Akiko Inomata; Akio Ogata; Dai Nakae
ARCHIVES OF TOXICOLOGY, Jan. 2014, [Reviewed]

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice
Jun'ichi Nakajima; Dai Nakae; Ken Yasukawa
JOURNAL OF PHARMACY AND PHARMACOLOGY, Aug. 2013, [Reviewed]

Effects of Maternal Exposure to Imazalil on Behavioral Development in F-1-Generation Mice
Toyohito Tanaka; Akio Ogata; Akiko Inomata; Dai Nakae
BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, Aug. 2013, [Reviewed]

Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems
Tatsuya Kato; Yukari Totsuka; Kousuke Ishino; Yoko Matsumoto; Yukie Tada; Dai Nakae; Sumio Goto; Shuichi Masuda; Sayaka Ogo; Masanobu Kawanishi; Takashi Yagi; Tomonari Matsuda; Masatoshi Watanabe; Keiji Wakabayashi
NANOTOXICOLOGY, Jun. 2013, [Reviewed]

Effects of maternal imazalil exposure on behavioral development in F₁-generation mice
TANAKA Toyohito; INOMATA Akiko; OGATA Akio; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2013

Long-term pulmonary responses to quadweekly intermittent intratracheal spray instillations of magnetite (Fe3O4) nanoparticles for 52 weeks in fischer 344 rats
Yukie Tada; Norio Yano; Hiroshi Takahashi; Katsuhiro Yuzawa; Hiroshi Ando; Yoshikazu Kubo; Akemichi Nagasawa; Akiko Inomata; Akio Ogata; Dai Nakae
Journal of Toxicologic Pathology, 2013, [Reviewed]

Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats
Jiegou Xu; Mitsuru Futakuchi; Hideo Shimizu; David B. Alexander; Kazuyoshi Yanagihara; Katsumi Fukamachi; Masumi Suzui; Jun Kanno; Akihiko Hirose; Akio Ogata; Yoshimitsu Sakamoto; Dai Nakae; Toyonori Omori; Hiroyuki Tsuda
CANCER SCIENCE, Dec. 2012, [Reviewed]

Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats
Jiegou Xu; Mitsuru Futakuchi; Hideo Shimizu; David B. Alexander; Kazuyoshi Yanagihara; Katsumi Fukamachi; Masumi Suzui; Jun Kanno; Akihiko Hirose; Akio Ogata; Yoshimitsu Sakamoto; Dai Nakae; Toyonori Omori; Hiroyuki Tsuda
Cancer Science, Dec. 2012, [Reviewed]

Reproductive and Neurobehavioral Effects of Brilliant Blue FCF in Mice
Toyohito Tanaka; Osamu Takahashi; Akiko Inomata; Akio Ogata; Dai Nakae
BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, Dec. 2012, [Reviewed]

Teratogenicity of multi-wall carbon nanotube (MWCNT) in ICR mice
Tomoko Fujitani; Ken-ichi Ohyama; Akihiko Hirose; Tetsuji Nishimura; Dai Nakae; Akio Ogata
JOURNAL OF TOXICOLOGICAL SCIENCES, Feb. 2012, [Reviewed]

Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice
Atsumi Yamaguchi; Tomoko Fujitani; Ken-ichi Ohyama; Dai Nakae; Akihiko Hirose; Tetsuji Nishimura; Akio Ogata
JOURNAL OF TOXICOLOGICAL SCIENCES, Feb. 2012, [Reviewed]

Induction of mesothelioma by an intraperitoneal administration of 5 different
SAKAMOTO Yoshimitsu; OGATA Akio; MAENO Tomokazu; NISHIMURA Tetsuji; HIROSE Akihiko; KOSUGI Yuki; SUZUKI Tosinari; NAKAE Dai
Annual Meeting of the Japanese Society of Toxicology, 2012

Teratogenicity of multi-wall carbon nanotube in ICR mice
FUJITANI Tomoko; OHYAMA Ken-ichi; HIROSE Akihiko; NISHIMURA Tetsuji; NAKAE Dai; OGATA Akio
Annual Meeting of the Japanese Society of Toxicology, 2012

Carcinogen-induced thyroid proliferative lesions in Wistar Hannover GALAS rats with thyroid dysplasia
Masayoshi Abe; Seigo Hayashi; Koji Usuda; Soichiro Hagio; Satoshi Furukawa; Dai Nakae
Journal of Toxicologic Pathology, 2012, [Reviewed]

Acute phase pulmonary responses to a single intratracheal spray instillation of magnetite (Fe3O4) nanoparticles in fischer 344 rats
Yukie Tada; Norio Yano; Hiroshi Takahashi; Katsuhiro Yuzawa; Hiroshi Ando; Yoshikazu Kubo; Akemichi Nagasawa; Akio Ogata; Dai Nakae
Journal of Toxicologic Pathology, 2012, [Reviewed]

Cytotoxic effects of hydroxylated fullerenes on isolated rat hepatocytes via mitochondrial dysfunction
Yoshio Nakagawa; Toshinari Suzuki; Hidemi Ishii; Dai Nakae; Akio Ogata
ARCHIVES OF TOXICOLOGY, Nov. 2011, [Reviewed]

Lack of chronic toxicity and carcinogenicity of dietary administrated catechin mixture in Wistar Hannover GALAS rats
Midori Yoshida; Miwa Takahashi; Kaoru Inoue; Dai Nakae; Akiyoshi Nishikawa
JOURNAL OF TOXICOLOGICAL SCIENCES, Jun. 2011, [Reviewed]

Importance of Researches on Chronic Effects by Manufactured Nanomaterials
Akihiko Hirose; Atsuya Takagi; Tetsuji Nishimura; Hiroyuki Tsuda; Yoshimitsu Sakamoto; Akio Ogata; Dai Nakae; Okio Hino; Jun Kanno
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, Feb. 2011, [Reviewed]

Neurobehavioural effects of clothianidin in two-generation toxicity study in mice.
Tanaka Toyohito; Takahashi Osamu; Ohyama Ken-ichi; Ogata Akio; Nakae Dai
Annual Meeting of the Japanese Society of Toxicology, 2011

Parenteral paradichlorobenzene exposure reduces sperm production, alters sperm morphology and exhibits an androgenic effect in rats and mice
Osamu Takahashi; Norio Ohashi; Dai Nakae; Akio Ogata
FOOD AND CHEMICAL TOXICOLOGY, Jan. 2011, [Reviewed]

Low-dose carcinogenicity of 2-amino-3-methylimidazo[4,5-f ]quinoline in rats: Evidence for the existence of no-effect levels and a mechanism involving p21(Cip/WAF1)
Min Wei; Hideki Wanibuchi; Dai Nakae; Hiroyuki Tsuda; Satoru Takahashi; Masao Hirose; Yukari Totsuka; Masae Tatematsu; Shoji Fukushima
CANCER SCIENCE, Jan. 2011, [Reviewed]

Mitochondrial dysfunction and biotransformation of beta-carboline alkaloids, harmine and harmaline, on isolated rat hepatocytes
Yoshio Nakagawa; Toshinari Suzuki; Hidemi Ishii; Akio Ogata; Dai Nakae
CHEMICO-BIOLOGICAL INTERACTIONS, Dec. 2010, [Reviewed]

Proliferative and Nonproliferative Lesions of the Rat and Mouse Hepatobiliary System
Bob Thoolen; Robert R. Maronpot; Takanori Harada; Abraham Nyska; Colin Rousseaux; Thomas Nolte; David E. Malarkey; Wolfgang Kaufmann; Karin Kuettler; Ulrich Deschl; Dai Nakae; Richard Gregson; Michael P. Vinlove; Amy E. Brix; Bhanu Singh; Fiorella Belpoggi; Jerrold M. Ward
TOXICOLOGIC PATHOLOGY, Dec. 2010, [Reviewed]

Toxicological evaluation of l-proline in a 90-day feeding study with Fischer 344 rats
Y. Tada; N. Yano; H. Takahashi; K. Yuzawa; H. Ando; Y. Kubo; A. Nagasawa; N. Ohashi; A. Ogata; D. Nakae
Regulatory Toxicology and Pharmacology, Oct. 2010, [Reviewed]

Serum level of expressed in renal carcinoma (ERC)/mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT)
Yoshimitsu Sakamoto; Dai Nakae; Yoshiaki Hagiwara; Kanako Satoh; Norio Ohashi; Katsumi Fukamachi; Hiroyuki Tsuda; Akihiko Hirose; Tetsuji Nishimura; Okio Hino; Akio Ogata
JOURNAL OF TOXICOLOGICAL SCIENCES, Apr. 2010, [Reviewed]

Effects of maternal clothianidin exposure on behavioral development in F₁-generation mice
TANAKA Toyohito; TAKAHASHI Osamu; OISHI Shinshi; OHASHI Norio; NAKAE Dai; OGATA Akio
Annual Meeting of the Japanese Society of Toxicology, 2010

Increase in in Utero Exposure to a Migrant, 4,4 '-Butylidenebis(6-t-butyl-m-cresol), from Nitrile-Butadiene Rubber Gloves on Brain Aromatase Activity in Male Rats
Kanako Satoh; Ryouichi Nonaka; Dai Nakae; Akio Ogata
BIOLOGICAL & PHARMACEUTICAL BULLETIN, Jan. 2010, [Reviewed]

A 90-day Feeding Toxicity Study of L-Serine in Male and Female Fischer 344 Rats
Yukie Tada; Norio Yano; Hiroshi Takahashi; Katsuhiro Yuzawa; Hiroshi Ando; Yoshikazu Kubo; Akemichi Nagasawa; Keigi Chin; Yasuko Kawamata; Ryosei Sakai; Norio Ohashi; Akio Ogata; Dai Nakae
JOURNAL OF TOXICOLOGIC PATHOLOGY, 2010, [Reviewed]

Enhancement of lung carcinogenesis initiated with 4-(N-hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone by Ogg1 gene deficiency in female, but not male, mice
Maki Igarashi; Manabu Watanabe; Midori Yoshida; Kouichi Sugaya; Yoshifumi Endo; Nozomi Miyajima; Masayoshi Abe; Sumio Sugano; Dai Nakae
JOURNAL OF TOXICOLOGICAL SCIENCES, Apr. 2009, [Reviewed]

Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats
Yoshimitsu Sakamoto; Dai Nakae; Nobutaka Fukumori; Kuniaki Tayama; Akihiko Maekawa; Kiyoshi Imai; Akihiko Hirose; Tetsuji Nishimura; Norio Ohashi; Akio Ogata
JOURNAL OF TOXICOLOGICAL SCIENCES, Feb. 2009, [Reviewed]

Possible Involvement of Adaptation Mechanisms in the Achievement of an Ineffective Dose Range for the Carcinogenicity of Genotoxic Carcinogens
Nakae Dai; Wanibuchi Hideki; Konishi Yoichi; Fukushima Shoji
Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 20 Nov. 2008
Recent findings have indicated that there may be a practical threshold or an ineffective dose range for the carcinogenicity of genotoxic carcinogens. In male Fischer 344 rats given a 16-week chronic feeding administration of 0.0001-1ppm of N-nitrosodiethylamine (DEN), glutathione S-transferase placental form (GST-P)-positive liver preneoplasias developed at 0.1ppm or higher, but hepatic level of 8-oxoguanine (8-oxoG), an oxidative DNA damage, was not elevated even at 1ppm. In contrast, hepatic 8-oxoG level was elevated by a single intraperitoneal administration of 0.001-100mg/kg body weight of DEN within 6h and remained high within 72h, in a clear dose-dependent manner without any ineffective doses, and GST-P-positive preneoplasias correspondingly developed through the selection procedure. The 8-oxoG level was elevated also in extrahepatic organs within 6h but returned to the normal level within 72h. In a separate experiment, hepatic 8-oxoG level remained high even 18 weeks after 2 weekly intraperitoneal administrations of 100mg/kg body weight of DEN. The early prolonged elevation of 8-oxoG level in target organ DNA was similarly induced by heterocyclic amines and dimethylarsinic acid in association with the down-regulation of the Ogg1 gene encoding an 8-oxoG-specific repair enzyme. Taken together, it is suggested that adaptation mechanisms may be involved in the achievement of an ineffective dose range for the carcinogenicity of genotoxic carcinogens during their continuing exposure at sufficiently low level doses.

Toxic effects of L-aspartic acid at high dose levels on kidneys and salivary glands in Fischer 344 rats detected in a 90-day feeding study
Y. Tada; N. Yano; H. Takahashi; K. Yuzawa; H. Ando; Y. Kubo; A. Nagasawa; S. Uehara; A. Ogata; D. Nakae
FOOD AND CHEMICAL TOXICOLOGY, Aug. 2008, [Reviewed]

Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol
Masayoshi Abe; Koji Usuda; Seigo Hayashi; Izumi Ogawa; Satoshi Furukawa; Maki Igarashi; Dai Nakae
ARCHIVES OF TOXICOLOGY, Aug. 2008, [Reviewed]

Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol
Masayoshi Abe; Noriko Suzuki; Midori Yoshida; Koji Usuda; Satoshi Furukawa; Lekh Rai Junela; Tsutomu Okubo; Dai Nakae
FOOD AND CHEMICAL TOXICOLOGY, May 2008, [Reviewed]

Points to consider on the non-clinical safety evaluation of anticancer drugs
Dai Nakae; Horoshi Onodera; Osamu Fueki; Tsutomu Urano; Noriyuki Komiyama; Fumio Sagami; Shuichi Kai; Chihiro Nishimura; Tohru Inoue
JOURNAL OF TOXICOLOGICAL SCIENCES, May 2008, [Reviewed]

Ogg1欠損マウスにおけるNNK誘発肺増殖性病変のEGFR突然変異　　　　　　　　　　　　　　　
Feb. 2008

Effects of piperonyl butoxide on spontaneous behaviour in F₁ generation mice.
Tanaka Toyohito; Takahashi Osamu; Oishi Shinshi; Ogata Akio; Nakae Dai
Annual Meeting of the Japanese Society of Toxicology, 2008

Involvement of mutation-based inhibition of beta-catenin phosphorylation at ser33 in the malignant progression of lung (Pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine in male fischer 344 rats
Maki Igarashi; Midori Yoshida; Manabu Watanabe; Toshiyuki Yamada; Takuya Sakurai; Yoshifumi Endo; Nozomi Miyajima; Akihiko Maekawa; Tsuneyuki Oikawa; Sumio Sugano; Dai Nakae
LUNG, Sep. 2007, [Reviewed]

Effects of Oseltamivir phosphate (Tamiflu) and its metabolite (GS4071) on monoamine neurotransmission in the rat brain
Kanako Satoh; Ryouichi Nonaka; Akio Gata; Dai Nakae; Shin-Ichi Uehara
BIOLOGICAL & PHARMACEUTICAL BULLETIN, Sep. 2007, [Reviewed]

OGG1欠損マウスにおけるNNKの発がん性感受性(Lung Carcinogenesis Induced by NNK in Ogg1 Knockout Mice)　　　　　　　　　　　　　　　
五十嵐 麻希; 吉田 緑; 渡邉 学; 阿部 正義; 菅野 純夫; 中江 大
日本癌学会総会記事, Aug. 2007

Carcinogenicity of dimethylarsinic acid in Ogg1-deficient mice
Anna Kinoshita; Hideki Wanibuchi; Keiichirou Morimura; Min Wei; Dai Nakae; Tsuyoshi Arai; Osamu Minowa; Tetsuo Noda; Susumu Nishimura; Shoji Fukushima
CANCER SCIENCE, Jun. 2007, [Reviewed]

Expression of inducible nitric oxide (NO) synthase but not prevention by its gene ablation of hepatocarcinogenesis with fibrosis caused by a choline-deficient, L-amino acid-defined diet in rats and mice
Ayumi Denda; Wakashi Kitayama; Hideki Kishida; Nao Murata; Kazutoshi Tamura; Osamu Kusuoka; Masahiro Tsutsumi; Fumiko Nishikawa; Eiji Kita; Dai Nakae; Yoichi Konishi; Hiroki Kuniyasu
NITRIC OXIDE-BIOLOGY AND CHEMISTRY, Feb. 2007, [Reviewed]

OGG1遺伝子欠損マウスにおけるNNKの肺発がん性　　　　　　　　　　　　　　　
Jan. 2007

Preliminary evaluation of toxicologic and carcinogenic risks of copper gluconate in rats given multiple carcinogens
Masayoshi Abe; Noriko Suzuki; Midori Yoshida; Maki Igarashi; Koji Usuda; Satoshi Furukawa; Akihiko Maekawa; Lekh Raj Juneja; Tsutomu Okubo; Dai Nakae
Journal of Toxicologic Pathology, 10 Oct. 2006, [Reviewed]

N-nitrosobis(hydroxypropyl)amine(BHP)誘発肺増殖性病変の悪性化とβ-Catenin活性の相関についての検討　　　　　　　　　　　　　　　
Sep. 2006

ラット中期多臓器発がん性試験法を用いたカテキン及びグルコン酸銅の発がんリスクの評価　　　　　　　　　　　　　　　
Sep. 2006

コリン欠乏アミノ酸(CDAA)食によるマウス肝発がんに対するOgg1遺伝子欠損の修飾効果　　　　　　　　　　　　　　　
Sep. 2006

Methylation of neutral endopeptidase 24.11 promoter in rat hepatocellular carcinoma
F Uematsu; M Takahashi; M Yoshida; M Igarashi; D Nakae
CANCER SCIENCE, Jul. 2006, [Reviewed]

Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule
D Yamada; M Yoshida; YN Williams; T Fukami; S Kikuchi; M Masuda; T Maruyama; T Ohta; D Nakae; A Maekawa; T Kitamura; Y Murakami
MOLECULAR AND CELLULAR BIOLOGY, May 2006, [Reviewed]

Inhibition of putrescine Aminopropyltransferase influences rat liver regeneration
Masaki Kobayashi; Koichi Takao; Yasuo Shiota; Yoshiaki Sugita; Masakazu Takahashi; Dai Nakae; Keijiro Samejima
BIOLOGICAL & PHARMACEUTICAL BULLETIN, May 2006, [Reviewed]

Evaluation of effects of catechin and copper gluconate in a rat multi-organ carcinogenesis model
Abe Masayoshi; Suzuki Noriko; Yoshida Midori; Igarashi Maki; Usuda Kouji; Furukawa Satoshi; Uematsu Fumiyuki; Takahashi Masakazu; Maekawa Akihiko; Nakae Dai
Annual Meeting of the Japanese Society of Toxicology, 2006

Ｍｍｈ／ＯＧＧ１ノックアウトマウスにおけるｐｅｎｔａｃｈｌｏｒｏｐｈｅｎｏｌの肝発癌感受性
2006

雄性マウスにおけるNNK誘発肺発がん　　　　　　　　　　　　　　　
Dec. 2005

食品中金属類と食品中化学物質の複合による発がんリスクに関する実験的研究 カテキン及びグルコン酸銅を用いたラット中期多臓器発がん性試験法による検討(1)　　　　　　　　　　　　　　　
Dec. 2005

Mmh/OGG1ノックアウトマウスにおけるpentachlorophenolの肝発癌感受性　　　　　　　　　　　　　　　
Nov. 2005

Temporal correlation of pathology and DNA damage with gene expression in a choline-deficient model of rat liver injury
CL Powell; O Kosyk; BU Bradford; JS Parker; EK Lobenhofer; A Denda; F Uematsu; D Nakae; Rusyn, I
HEPATOLOGY, Nov. 2005, [Reviewed]

Expression of profiles of cytochrome P450 enzymes in the uterus and liver of female rats treated with indole-3-carbinol(Liver, Alimentary system, Proceedings of the 32nd Annual Meeting)
YOSHIDA Midori; NAKAE Dai; MAEKAWA Akihiko
Journal of toxicological sciences, 31 Oct. 2005
Effects of estrogenic endocrine disrupting chemicals (EDCs) on the female reproductive tract, in addition to uterine carcinogenesis, in rats exposed at adulthood or perinatal period were investigated. In adult normal cycling and ovariectomized (OVX) rats, high dose exposure to p-tert octylphenol (OP) directly exerted estrogenic activity on the uterus and vagina, the minimum effective level being lower in OVX rats than normal cycling ones. Serum concentrations of OP were detected at similar levels in both normal cycling and OVX rats and the effects increased with a dose- and time-dependent manner, indicating that the OVX rats are more sensitive for detection of estrogenic activity of chemicals. Neonatal exposure to high dose OP showed irreversible effects on the female reproductive tract of rats. Various effects such as persistent estrus, atrophic and polycystic ovary and luminal-epithelial hyperplasia were considered to be due to disruption of the hypothalamus-pituitary-gonadal control system, whereas the inhibition of uterine gland-genesis might be direct estrogenic action of OP. Our data of perinatal or adulthood exposure to high dose estrogenic EDCs with or without carcinogen using Donryu rats provided that the EDCs promoted uterine carcinogenesis in rats.

新規抗酸化物質4-hydroxyphenyl N-tert-butyl nitroneのラットにおける内因性肝細胞がん誘発に対する抑制効果　　　　　　　　　　　　　　　
Sep. 2005

ラット肺腺がんの発生過程におけるβ-カテニンの変化に関する検索　　　　　　　　　　　　　　　
Sep. 2005

ラットにおけるコリン欠乏アミノ酸食前処置のaminophenylnorharmanの肝臓および大腸発がん性に及ぼす影響　　　　　　　　　　　　　　　
Sep. 2005

Distinct patterns of gene expression in hepatocellular carcinomas and adjacent non-cancerous, cirrhotic liver tissues in rats fed a choline-deficient, L-amino acid-defined diet
F Uematsu; M Takahashi; M Yoshida; M Igarashi; N Watanabe; N Suzuki; M Abe; Rusyn, I; RA Floyd; D Nakae
CANCER SCIENCE, Jul. 2005, [Reviewed]

Exercise training enhances tumor necrosis factor-alpha-induced expressions of anti-apoptotic genes without alterations in caspase-3 activity in rat epididymal adipocytes
T Sakurai; M Takei; J Ogasawara; N Watanabe; M Sanpei; M Yoshida; D Nakae; T Sakurai; N Nakano; T Kizaki; H Ohno; T Izawa
JAPANESE JOURNAL OF PHYSIOLOGY, Jun. 2005, [Reviewed]

Lack elf potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver
S Fukushima; H Wanibuchi; K Morimura; D Nakae; H Tsuda; K Imaida; T Shirai; M Tatematsu; T Tsukamoto; M Hirose; F Furukawa
CANCER LETTERS, May 2005, [Reviewed]

Differentially altered protein expression profiles with early phase hepatocarcinogenesis in Nagase analbuminemic rats and Sprague-Dawley rat by 3'-Me-DAB
A. H.; T. M.; U. F.; I. M.; A. M.; Y. M.; M. A.; M. M.; N. D.
Japan Journal of Molecular Tumor Marker Research, 2005

α-smooth muscle actin-positive stromal cells reactive to estrogens surround endometrial glands in rats but not mice
Takasumi Shimomoto; Midori Yoshida; Shin-Ichi Katsuda; Masakazu Takahashi; Fumiyuki Uematsu; Hiroki Kuniyasu; Akihiko Maekawa; Dai Nakae
Journal of Toxicologic Pathology, 2005, [Reviewed]

Nitric oxide production by primary liver cells isolated from amino acid diet-fed rats
Y Kotake; H Kishida; D Nakae; RA Floyd
NITRIC OXIDE, PT E, 2005, [Reviewed]

Induction of DNA-adducts and increase of 8-hydroxy-2-deoxyguanosine, but no development of preneoplastic lesions in offspring liver with transplacental and trans-breast milk exposure to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) in rats
T Ichihara; H Wanibuchi; Y Totsuka; K Morimura; M Wei; D Nakae; S Fukushima
CANCER SCIENCE, Dec. 2004, [Reviewed]

Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N '-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism
M Yoshida; S Katashima; J Ando; T Tanaka; F Uematsu; D Nakae; A Maekawa
CARCINOGENESIS, Nov. 2004, [Reviewed]

Effects of estrogens and metabolites on endometrial carcinogenesis in young adult mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine
M Takahashi; T Shimomoto; K Miyajima; M Yoshida; S Katashima; F Uematsu; A Maekawa; D Nakae
CANCER LETTERS, Jul. 2004, [Reviewed]

Chemopreventive effects of hydroxymatairesinol on uterine carcinogenesis in Donryu rats
S Katsuda; M Yoshida; N Saarinen; A Smeds; D Nakae; R Santti; A Maekawa
EXPERIMENTAL BIOLOGY AND MEDICINE, May 2004, [Reviewed]

Lack of toxicity or carcinogenicity of S-170, a sucrose fatty acid ester, in F344 rats
M Yoshida; S Katsuda; D Nakae; A Maekawa
FOOD AND CHEMICAL TOXICOLOGY, Apr. 2004, [Reviewed]

Inhibition of the development of hepatocellular carcinomas by phenyl N-tert-butyl nitrone in rats fed with a choline-deficient, L-amino acid-defined diet
D Nakae; F Uematsu; H Kishida; O Kusuoka; S Katsuda; M Yoshida; M Takahashi; A Maekawa; A Denda; Y Konishi; Y Kotake; RA Floyd
CANCER LETTERS, Mar. 2004, [Reviewed]

A case report of a choroid plexus carcinoma spontaneously occurring in the right lateral ventricle of a 14-week-old, female Donryu rat
T Shimomoto; M Yoshida; M Takahashi; F Uematsu; A Maekawa; D Nakae
TOXICOLOGIC PATHOLOGY, Mar. 2004, [Reviewed]

α-Naphthylisothiocyanate Induces Intrahepatic Bile Duct with Greater Proliferation in Female Rats than in Males
Fumiyuki Uematsu; Midori Yoshida; Masakazu Takahashi; Masayoshi Abe; Maki Igarashi; Naoto Watanabe; Noriko Suzuki; Akihiko Maekawa; Dai Nakae
Journal of Toxicologic Pathology, 2004, [Reviewed]

Post-initiation inhibition of MeIQx hepatocarcinogenesis in rats by cysteine.
Ogawa M; Wanibuchi H; Nishkawa T; Yano Y; Otani S; Totsuka Y; Wakabayashi K; Nakae D; Fukushima S
Osaka city medical journal, Jun. 2003, [Reviewed]
Rats were administered cysteine at a dose of 100 mg/kg b.w. 5 times per week after 2-amino-3, 8-dimethylimidazo [4,5-f] quinoxaline (MeIQx) treatment. Significant decrease in numbers and areas of glutathione S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, and silver-stained nucleolar organizer regions were evident in the livers of rats treated with cysteine after MeIQx treatment. Morever, post-initiation stage cysteine treatment resulted in decreased hepatic insulin-like growth factor (IGF)-I mRNA expression. Thus post-initiation cysteine treatment may exert chemopreventive effect on MeIQx hepatocarcinogenesis.

Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
S Fukushima; H Wanibuchi; K Morimura; M Wei; D Nakae; Y Konishi; H Tsuda; N Takasuka; K Imaida; T Shirai; M Tatematsu; T Tsukamoto; M Hirose; F Furukawa
CANCER LETTERS, Feb. 2003, [Reviewed]

Effects of maternal exposure to nonylphenol on growth and development of the female reproductive system and uterine carcinogenesis in rats.
Yoshida, M; Shimomoto, T; Katashima, S; Shirai, T; Nakae, D; Watanabe, G; Taya, K; Maekawa, A
J Toxicol Pathol, 2003, [Reviewed]

Value of GST-P positive preneoplastic hepatic foci in dose-response studies of hepatocarcinogenesis: Evidence for practical thresholds with both genotoxic and nongenotoxic carcinogens. A review of recent work
H Tsuda; S Fukushima; H Wanibuchi; K Morimura; D Nakae; K Imaida; M Tatematsu; M Hirose; K Wakabayashi; MA Moore
TOXICOLOGIC PATHOLOGY, Jan. 2003, [Reviewed]

Effects of phenyl N-tert-butyl nitrone and its derivatives on the early phase of hepatocarcinogenesis in rats fed a choline-deficient, L-amino acid-defined diet
D Nakae; H Kishida; T Enami; Y Konishi; KL Hensley; RA Floyd; Y Kotake
CANCER SCIENCE, Jan. 2003, [Reviewed]

Induction of different types of uterine adenocarcinomas in Donryu rats due to neonatal exposure to high-dose p-t-octylphenol for different periods
M Yoshida; S Katsuda; T Tanimoto; S Asai; D Nakae; Y Kurokawa; K Taya; A Maekawa
CARCINOGENESIS, Oct. 2002, [Reviewed]

Lack of a dose-response relationship for carcinogenicity in the rat liver with low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-nitrosodiethylamine
S Fukushima; H Wanibuchi; K Morimura; M Wei; D Nakae; Y Konishi; H Tsuda; N Uehara; K Imaida; T Shirai; M Tatematsu; T Tsukamoto; M Hirose; F Furukawa; K Wakabayashi; Y Totsuka
JAPANESE JOURNAL OF CANCER RESEARCH, Oct. 2002, [Reviewed]

Inhibitory effects of lemon grass (Cymbopogon citratus, Stapf) extract on the early phase of hepatocarcinogenesis after initiation with diethylnitrosamine in male Fischer 344 rats
R Puatanachokchai; H Kishida; A Denda; N Murata; Y Konishi; U Vinitketkumnuen; D Nakae
CANCER LETTERS, Sep. 2002, [Reviewed]

Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors
M Wei; H Wanibuchi; K Morimura; S Iwai; K Yoshida; G Endo; D Nakae; S Fukushima
CARCINOGENESIS, Aug. 2002, [Reviewed]

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S-transferase placental form positive foci: A possible reactive oxygen species mechanism
T Nishikawa; H Wanibuchi; M Ogawa; A Kinoshita; K Morimura; T Hiroi; Y Funae; H Kishida; D Nakae; S Fukushima
INTERNATIONAL JOURNAL OF CANCER, Jul. 2002, [Reviewed]

Alterations of the Fhit gene in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats
T Tsujiuchi; Y Sasaki; T Kubozoe; M Tsutsumi; Y Konishi; D Nakae
MOLECULAR CARCINOGENESIS, May 2002, [Reviewed]

Reactive oxygen species in choline deficiency induced carcinogenesis and nitrone inhibition
RA Floyd; Y Kotake; K Hensley; D Nakae; Y Konishi
MOLECULAR AND CELLULAR BIOCHEMISTRY, May 2002, [Reviewed]

Immunohistochemical detection of a substituted 1,N-2-ethenodeoxyguanosine adduct by omega-6 polyunsaturated fatty acid hydroperoxides in the liver of rats fed a choline-deficient, L-amino acid-defined diet
Y Kawai; Y Kato; D Nakae; O Kusuoka; Y Konishi; K Uchida; T Osawa
CARCINOGENESIS, Mar. 2002, [Reviewed]

Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet
A Denda; WA Kitayama; H Kishida; N Murata; M Tsutsumi; T Tsujiuchi; D Nakae; Y Konishi
JAPANESE JOURNAL OF CANCER RESEARCH, Feb. 2002, [Reviewed]

Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide
A Denda; W Kitayama; A Murata; H Kishida; Y Sasaki; O Kusuoka; T Tsujiuchi; M Tsutsumi; D Nakae; H Takagi; Y Konishi
CARCINOGENESIS, Feb. 2002, [Reviewed]

Lack of promoting effect due to oral administration of dimethylarsinic acid on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine
N Seike; H Wanibuchi; K Morimura; T Nishikawa; H Kishida; D Nakae; K Hirata; S Fukushima
CANCER LETTERS, Jan. 2002, [Reviewed]

Reactive Oxygen and Nitrogen Oxide Species-induced Stress, a Major Intrinsic Factor Involved in Carcinogenic Processes and a Possible Target for Cancer Prevention.
Nakae D; Umemura T; Kurokawa Y
Asian Pacific journal of cancer prevention : APJCP, 2002, [Reviewed]
Reactive oxygen and nitrogen oxide species and their inducing stress are involved in a variety of physiological and pathological phenomena in aerobes, including humans. For multistage carcinogenic processes, reactive oxygen and nitrogen oxide species-induced stress (RONOSS) serves as a major intrinsic factor and is involved in every step. This means that free radicals, RONOSS and their inducing downstream events may be targets for cancer prevention. It is therefore of importance to elucidate the mechanisms underlying the participation of RONOSS in carcinogenesis and to apply the obtained results for establishment of strategies to control cancer development. Despite the large body of accumulated knowledge due to worldwide efforts dealing with this research field, there still remain numerous uncertainties. In this mini-review, we introduce two examples of such efforts, one concerning a renal carcinogen KBrO(3) and the other dealing with hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet, in order to give some idea about the current understanding of the roles of RONOSS in carcinogenesis.

The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells
J Yoshi; H Yoshiji; S Kuriyama; Y Ikenaka; R Noguchi; H Okuda; H Tsujinoue; T Nakatani; H Kishida; D Nakae; DE Gomez; MS De Lorenzo; AM Tejera; H Fukui
INTERNATIONAL JOURNAL OF CANCER, Dec. 2001, [Reviewed]

Increased oxidative DNA damage in mammary tumor cells by continuous epidermal growth factor stimulation
Jun Ichi Hamada; Daichi Nakata; Dai Nakae; Yozo Kobayashi; Hiroyuki Akai; Yoichi Konishi; Futoshi Okada; Toshiyuki Shibata; Masuo Hosokawa; Tetsuya Moriuchi
Journal of the National Cancer Institute, 07 Feb. 2001

Elevated expression of transforming growth factor βs and the tumor necrosis factor family in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats
T. Tsujiuchi; Y. Sasaki; N. Murata; M. Tsutsumi; D. Nakae; Y. Konishi
Experimental and Toxicologic Pathology, 2001, [Reviewed]

FHIT alterations in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats
Tsujiuchi Tsujiuchi; Yasutaka Sasaki; Nao Murata; Masahiro Tsutsumi; Yoichi Konishi; Dai Nakae
Carcinogenesis, 2001, [Reviewed]

Interleukin-15 expression is associated with malignant potential in colon cancer cells
Hiroki Kuniyasu; Naohide Oue; Dai Nakae; Masahiro Tsutsumi; Ayumi Denda; Toshifumi Tsujiuchi; Hiroshi Yokozaki; Wataru Yasui
Pathobiology, 2001, [Reviewed]

Enhancement of hepatocarcinogenesis initiated with diethylnitrosamine or N-nitrosobis(2-hydroxypropyl)amine by a choline-deficient, L-amino acid-defined diet administered prior to the carcinogen exposure in rats
H Kishida; D Nakae; Y Kobayashi; O Kusuoka; W Kitayama; A Denda; H Fukui; Y Konishi
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, Oct. 2000, [Reviewed]

Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria
K Hensley; Y Kotake; H Sang; QN Pye; GL Wallis; LM Kolker; T Tabatabaie; CA Stewart; Y Konishi; D Nakae; RA Floyd
CARCINOGENESIS, May 2000, [Reviewed]

Hepatotoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice
M Yoshida; K Miyajima; K Shiraki; J Ando; K Kudoh; D Nakae; M Takahashi; A Maekawa
CANCER LETTERS, Jul. 1999, [Reviewed]

Inflammatory cell mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative enzymes in murine fibrosarcoma cells
F. Okada; K. Nakai; T. Kobayashi; T. Shibata; S. Tagami; Y. Kawakami; T. Kitazawa; R. Kominami; S. Yoshimura; K. Suzuki; N. Taniguchi; O. Inanami; M. Kuwabara; H. Kishida; D. Nakae; Y. Konishi; T. Moriuchi; M. Hosokawa
British Journal of Cancer, 1999

Single treatment with cisplatin or UFT, but not their combination treatment enhances the metastatic capacity of mouse fibrosarcoma cells
Sungki Choi; Futoshi Okada; Masanobu Kobayashi; Hasem Habelhah; Dai Nakae; Yoichi Konishi; Yasunori Totsuka; Masuo Hosokawa
Anti-Cancer Drugs, 1999, [Reviewed]

Inhibition by phenyl N-tert-butyl nitrone of early phase carcinogenesis in the livers of rats fed a choline-deficient, L-amino acid-defined diet
Dai Nakae; Yashige Kotake; Hideki Kishida; Kenneth L. Hensley; Ayumi Denda; Yozo Kobayashi; Wakashi Kitayama; Toshifumi Tsujiuchi; Hong Sang; Charles A. Stewart; Tahereh Tabatabaie; Robert A. Floyd; Yoichi Konishi
Cancer Research, 15 Oct. 1998, [Reviewed]

Prevention by 1'-acetoxychavicol acetate of the induction but not growth of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet
Yozo Kobayashi; Dai Nakae; Hiroyuki Akai; Hideki Kishida; Eijiro Okajima; Wakashi Kitayama; Ayumi Denda; Toshifumi Tsujiuchi; Akira Murakami; Koichi Koshimizu; Hajime Ohigashi; Yoichi Konishi
Carcinogenesis, Oct. 1998, [Reviewed]

Increased telomerase activity in intrahepatic cholangiocellular carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters
Katsumichi Iki; Toshifumi Tsujiuchi; Toshimitsu Majima; Hiroyuki Sakitani; Masahiro Tsutsumi; Makoto Takahama; Masatoshi Yoshimoto; Dai Nakae; Tsukasa Tsunoda; Yoichi Konishi
Cancer Letters, 25 Sep. 1998, [Reviewed]

Prevention by inhibitors of arachidonic acid cascade of liver carcinogenesis, cirrhosis and oxidative DNA damage caused by a choline- deficient, L-amino acid-defined diet in rats
Ayumi Denda; Takehiro Endoh; Qing Tang; Toshifumi Tsujiuchi; Dai Nakae; Yoichi Konishi
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 18 Jun. 1998, [Reviewed]

Increased telomerase activity and absence of p53 mutation in oligo-astrocytomas induced by N-ethyl-N-nitrosourea in rats
Hiroyuki Sakitani; Toshifumi Tsujiuchi; Kunihiko Kobitsu; Akira Kido; Katsumichi Iki; Makoto Takahama; Mitsuhiro Nakamura; Toshisuke Sakaki; Dai Nakae; Yoichi Konishi; Masahiro Tsutsumi
Cancer Letters, 24 Apr. 1998, [Reviewed]

Inhibition of early-phase exogenous and endogenous liver carcinogenesis in transgenic rats harboring a rat glutathione S-transferase placental form gene
Dai Nakae; Ayumi Denda; Yozo Kobayashi; Hiroyuki Akai; Hideki Kishida; Toshifumi Tsujiuchi; Yoichi Konishi; Toshiya Suzuki; Masami Muramatsu
Japanese Journal of Cancer Research, 1998, [Reviewed]

Systemic mast cell disease with splenic infarction: A case report
Hiroshi Maruyama; Seiichi Sugihara; Kyoko Ishihara; Kazuo Sada; Masahiro Tsutsumi; Toshifumi Tsujiuchi; Dai Nakae; Yoichi Konishi
Pathology International, 1998, [Reviewed]

Inhibition by N-(4-hydroxyphenyl)retinamide and all-trans-retinoic acid of exogenous and endogenous development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in the livers of rats
Kazutoshi Tamura; Dai Nakae; Kohsuke Horiguchi; Hiroyuki Akai; Yozo Kobayashi; Nobuaki Andoh; Hiroshi Satoh; Ayumi Denda; Toshifumi Tsujiuchi; Hitoshi Yoshiji; Yoichi Konishi
Carcinogenesis, Nov. 1997, [Reviewed]

Inhibition by piroxicam of oxidative DNA damage, liver cirrhosis and development of enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats
Ayumi Denda; Takehiro Endoh; Wakashi Kitayama; Qing Tang; Osamu Noguchi; Yozoh Kobayashi; Hiroyuki Akai; Eijiroh Okajima; Toshifumi Tsujiuchi; Masahiro Tsutsumi; Dai Nakae; Yoichi Konishi
Carcinogenesis, Oct. 1997, [Reviewed]

Involvement of 8-hydroxyguanine formation in the initiation of rat liver carcinogenesis by low dose levels of N-nitrosodiethylamine
D Nakae; Y Kobayashi; H Akai; N Andoh; H Satoh; K Ohashi; M Tsutsumi; Y Konishi
CANCER RESEARCH, Apr. 1997, [Reviewed]

Chronic toxicity and carcinogenicity studies of 2-methylnaphthalene in B6C3F1 mice
Yoshiaki Murata; Ayumi Denda; Hiroshi Maruyama; Dai Nakae; Masahiro Tsutsumi; Toshifumi Tsujiuchi; Yoichi Konishi
Fundamental and Applied Toxicology, 1997, [Reviewed]

Inhibition by green tea extract of diethylnitrosamine-initiated but not choline-deficient, L-amino acid-defined diet-associated development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in rat liver
Kazutoshi Tamura; Dai Nakae; Kohsuke Horiguchi; Hiroyuki Akai; Yozo Kobayashi; Hiroshi Satoh; Toshifumi Tsujiuchi; Ayumi Denda; Yoichi Konishi
Japanese Journal of Cancer Research, 1997, [Reviewed]

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats
Toshifumi Tsujiuchi; Akira Kido; Dai Nakae; Makoto Takahama; Toshimitsu Majima; Kunihiko Kobitsu; Eijiro Okajima; Masahiro Tsutsumi; Ayumi Denda; Yoichi Konishi
Cancer Letters, 12 Nov. 1996, [Reviewed]

Increased telomerase activities in hyperplastic nodules and hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats
T Tsujiuchi; M Tsutsumi; K Kobitsu; T Majima; A Denda; D Nakae; Y Konishi
RECENT ADVANCES IN GASTROENTEROLOGICAL CARCINOGENESIS I, 1996, [Reviewed]

Effects of inhibitors of arachidonic acid cascade on the liver carcinogenesis by a choline-deficient, L-amino acid-defined diet in rats
A Denda; T Endoh; Q Tang; T Tsujiuchi; D Nakae; Y Konishi
RECENT ADVANCES IN GASTROENTEROLOGICAL CARCINOGENESIS I, 1996, [Reviewed]

Inhibition by N-(4-hydroxyphenyl) retinamide of exogenous and endogenous liver carcinogenesis in rats
D Nakae; K Tamura; H Akai; Y Kobayashi; K Horiguchi; A Denda; Y Konishi
RECENT ADVANCES IN GASTROENTEROLOGICAL CARCINOGENESIS I, 1996, [Reviewed]

Inhibition by acetylsalicylic acid, a cyclo-oxygenase inhibitor, and p-bromophenacylbromide, a phospholipase A2 inhibitor, of both cirrhosis and enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats
Takehiro Endoh; Qing Tang; Ayumi Denda; Osamu Noguchi; Eisaku Kobayashi; Kazutoshi Tamura; Kohsuke Horiguchi; Hiroyuki Ogasawara; Toshifumi Tsujiuchi; Dai Nakae; Masahito Sugimura; Yoichi Konishi
Carcinogenesis, 1996, [Reviewed]

Inhibitory effects of N,N′-diphenyl-p-phenylenediamine on the early stage of the enhanced hepatocarcinogenesis caused by coadministration of ethionine and a choline-deficient L-amino acid-defined diet in rats
Eisaku Kobayashi; Toshifumi Tsujiuchi; Dai Nakae; Yasushi Mizumoto; Nobuaki Andoh; Takehiro Endoh; Hiromichi Kitada; Masahiro Tsutsumi; Ayumi Denda; Yoichi Konishi
Experimental and Toxicologic Pathology, 1996, [Reviewed]

Increased telomerase activity in hyperplastic nodules and hepatocellular carcinomas induced by a choline-deficient L-amino acid-defined diet in rats
Toshifumi Tsujiuchi; Masahiro Tsutsumi; Akira Kido; Kunihiko Kobitsu; Makoto Takahama; Toshimitsu Majima; Ayumi Denda; Dai Nakae; Yoichi Konishi
Japanese Journal of Cancer Research, 1996, [Reviewed]

Prevention by methionine of enhancement of hepatocarcinogenesis by coadministration of a choline-deficient l-amino acid-defined diet and ethionine in rats
Toshifumi Tsujiuchi; Eisaku Kobayashi; Dai Nakae; Yasushi Mizumoto; Nobuaki Andoh; Hiromichi Kitada; Kazuo Ohashi; Tomokazu Fukuda; Akira Kido; Masahiro Tsutsumi; Ayumi Denda; Yoichi Konishi
Japanese Journal of Cancer Research, Dec. 1995, [Reviewed]

IMPROVED GENOMIC NUCLEAR-DNA EXTRACTION FOR 8-HYDROXYDEOXYGUANOSINE ANALYSIS OF SMALL AMOUNTS OF RAT-LIVER TISSUE
D NAKAE; Y MIZUMOTO; E KOBAYASHI; O NOGUCHI; Y KONISHI
CANCER LETTERS, Nov. 1995, [Reviewed]

Comparative changes in the liver of female Fischer-344 rats after short- term feeding of a semipurified or a semisynthetic L-amino acid-defined choline-deficient diet
D. Nakae; Y. Mizumoto; N. Andoh; K. Tamura; K. Horiguchi; T. Endoh; E. Kobayashi; T. Tsujiuchi; A. Denda; B. Lombardi; Y. Konishi
Toxicologic Pathology, 1995, [Reviewed]

PROTECTION AGAINST LIPID-PEROXIDATION INDUCED DURING PRESERVATION OF LUNGS FOR TRANSPLANTATION
K NEZU; K KUSHIBE; T TOJO; N SAWABATA; K KAWACHI; Y MIZUMOTO; D NAKAE; Y KONISHI; S KITAMURA
JOURNAL OF HEART AND LUNG TRANSPLANTATION, Nov. 1994, [Reviewed]

CLINICAL CHARACTERISTICS AND PROLIFERATING ACTIVITY OF INTRAHEPATIC CHOLANGIOCARCINOMA
K OHASHI; Y NAKAJIMA; M TSUTSUMI; H KANEHIRO; T FUKUOKA; M HISANAGA; J TAKI; D NAKAE; Y KONISHI; H NAKANO
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Sep. 1994, [Reviewed]

SELECTIVE 8-HYDROXYGUANINE FORMATION IN PANCREATIC DNA DUE TO A SINGLE INTRAVENOUS ADMINISTRATION OF 4-HYDROXYAMINOQUINOLINE 1-OXIDE IN RATS
D NAKAE; N ANDOH; Y MIZUMOTO; T ENDOH; N SHIMOJI; K HORIGUCHI; K SHIRAIWA; K TAMURA; A DENDA; Y KONISHI
CANCER LETTERS, Aug. 1994, [Reviewed]

Prevention by acetylsailcylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, l-amino acid-defined diet in rats
Ayumi Denda; Qing Tang; Takehiro Endoh; Toshifumi Tsujiuchi; Kohsuke Horiguchi; Osamu Noguchi; Yasushi Mizumoto; Dai Nakae; Yoichi Konishi
Carcinogenesis, Jun. 1994, [Reviewed]

DIFFERENT ROLES OF 8-HYDROXYGUANINE FORMATION AND 2-THIOBARBITURIC ACID-REACTING SUBSTANCE GENERATION IN THE EARLY PHASE OF LIVER CARCINOGENESIS INDUCED BY A CHOLINE-DEFICIENT, L-AMINO ACID-DEFINED DIET IN RATS
D NAKAE; Y MIZUMOTO; H YOSHIJI; N ANDOH; K HORIGUCHI; K SHIRAIWA; E KOBAYASHI; T ENDOH; N SHIMOJI; K TAMURA; T TSUJIUCHI; A DENDA; Y KONISHI
JAPANESE JOURNAL OF CANCER RESEARCH, May 1994, [Reviewed]

Inhibitory effects of 2-o-octadecylascorbic acid and other vitamin C and e derivatives on the induction of enzyme-altered putative preneoplastic lesions in the livers of rats fed a choline-deficient, l-amino acid-defined diet
Yasushi Mizumoto; Dai Nakae; Hitoshi Yoshiji; Nobuaki Andoh; Kohsuke Horiguchi; Takehiro Endoh; Eisaku Kobayashi; Toshifumi Tsujiuchi; Naoshi Shimoji; Ayumi Denda; Tadasu Tsujii; Minako Nagao; Keiji Wakabayashi; Yoichi Konishi
Carcinogenesis, Feb. 1994, [Reviewed]

DISSOCIATED INHIBITORY EFFECTS OF N,N'-DIPHENYL-P-PHENYLENEDIAMINE, ON RAT-LIVER CARCINOGENESIS BY A CHOLINE-DEFICIENT L-AMINO-ACID DEFINED DIET
D NAKAE; Y MIZUMOTO; N ANDOH; T ENDOH; E KOBAYASHI; T TSUJIUCHI; A DENDA; Y KONISHI
FRONTIERS OF REACTIVE OXYGEN SPECIES IN BIOLOGY AND MEDICINE, 1994, [Reviewed]

PREVENTION BY INHIBITORS OF ARACHIDONIC-ACID (AA) METABOLISM OF LIVER-CIRRHOSIS AND CARCINOGENESIS CAUSED BY CHOLINE-DEFICIENT L-AMINO ACID-DEFINED (CDAA) DIET ASSOCIATED WITH THEIR INHIBITION OF THE INDUCTION OF LIPID-PEROXIDATION AND 8-HYDROXYDEOXYGUANOSINE (8-OHDG)
A DENDA; T ENDOH; Q TANG; T TSUJIUCHI; O NOGUCHI; N ANDOH; Y MIZUMOTO; D NAKAE; Y KONISHI
FRONTIERS OF REACTIVE OXYGEN SPECIES IN BIOLOGY AND MEDICINE, 1994, [Reviewed]

Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of rat hepatocarcinogenesis
Ayumi Denda; Qing Tang; Toshifumi Tsujiuchi; Masahiro Tsutsumi; Toshihiro Amanuma; Yoshiharu Murata; Kazutoshi Tamura; Konsuke Horiguchi; Dai Nakae; Yoichi Konishi
Carcinogenesis, Jan. 1993, [Reviewed]

POSSIBLE ENHANCING EFFECT OF THE IMMUNOSUPPRESSIVE AGENT, 6-MERCAPTOPURINE(6-MP) ON FOCAL LESION DEVELOPMENT IN CIRRHOTIC LIVER INDUCED BY CARBON-TETRACHLORIDE BUT NOT FURFURAL IN F344 RATS
H MARUYAMA; T AMANUMA; Y TAKASHIMA; H YOSHIJI; D NAKAE; M TSUTSUMI; T TSUJIUCHI; A DENDA; Y KONISHI
CARCINOGENESIS, Aug. 1992, [Reviewed]

INHIBITION OF OXY RADICALS MEDIATED LIVER CARCINOGENESIS BY DIETARY IRON-DEFICIENCY IN RATS GIVEN A CHOLINE-DEFICIENT L-AMINO-ACID DEFINED (CDAA) DIET
D NAKAE; Y MIZUMOTO; H YOSHIJI; K HORIGUCHI; A DENDA; Y KONISHI
OXYGEN RADICALS, 1992, [Reviewed]

INHIBITORY EFFECT OF DIETARY IRON-DEFICIENCY ON THE INDUCTION OF PUTATIVE PRENEOPLASTIC FOCI IN RAT-LIVER INITIATED WITH DIETHYLNITROSAMINE AND PROMOTED BY PHENOBARBITAL
H YOSHIJI; D NAKAE; T KINUGASA; M MATSUZAKI; A DENDA; T TSUJII; Y KONISHI
BRITISH JOURNAL OF CANCER, Nov. 1991, [Reviewed]

Effects of catechol and its analogs on pancreatic carcinogenesis initiated by n-nitrosobis(2-oxopropyl)amine in syrian hamsters
Hiroshi Maruyama; Toshihiro Amanuma; Dai Nakae; Masahiro Tsutsumi; Satoshi Kondo; Toshifumi Tsujiuchi; Ayumi Denda; Yoichi Konishi
Carcinogenesis, Jul. 1991, [Reviewed]

Induction of 8-hydroxydeoxyguanosine but not initiation of carcinogenesis by redox enzyme modulations with or without menadione in rat liver
Ayumi Denda; Kimie Sai; Qing Tang; Toshifumi Tsujiuchi; Masahiro Tsutsumi; Toshihiro Amanuma; Yoshiharu Murata; Dai Nakae; Hiroshi Maruyama; Yuji Kurokawa; Yoichi Konishi
Carcinogenesis, Apr. 1991, [Reviewed]

POSSIBLE INVOLVEMENT OF POLY-ADP-RIBOSYLATION IN PHENOBARBITAL PROMOTION OF RAT HEPATOCARCINOGENESIS
T TSUJIUCHI; M TSUTSUMI; A DENDA; S KONDOH; D NAKAE; H MARUYAMA; Y KONISHI
CARCINOGENESIS, Oct. 1990, [Reviewed]

INFLUENCE OF TIMING OF ADMINISTRATION OF LIPOSOME-ENCAPSULATED SUPEROXIDE-DISMUTASE ON ITS PREVENTION OF ACETAMINOPHEN-INDUCED LIVER-CELL NECROSIS IN RATS
D NAKAE; H YOSHIJI; K YAMAMOTO; H MARUYAMA; T KINUGASA; Y TAKASHIMA; A DENDA; Y KONISHI
ACTA PATHOLOGICA JAPONICA, Aug. 1990, [Reviewed]

LIPOSOME-ENCAPSULATED SUPEROXIDE-DISMUTASE PREVENTS LIVER NECROSIS INDUCED BY ACETAMINOPHEN
D NAKAE; K YAMAMOTO; H YOSHIJI; T KINUGASA; H MARUYAMA; JL FARBER; Y KONISHI
AMERICAN JOURNAL OF PATHOLOGY, Apr. 1990, [Reviewed]

Protective effect of liposome-encapsulated superoxide dismutase on acetaminophen-induced rat hepatocellular necrosis.
YOSHIJI Hitoshi; NAKAE Dai; SHIRAIWA Kazumi; TSUJII Tadasu; KONISHI Yoichi
Kanzo, 1990
Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) pratected acetaminophen (APAP)-induced liver cell necrosis, whereas liposome, free superoxide dismutase or heat denatured SOD encapsulated into liposome had no such an effect in Sprague-Dawley rats. LSOD did not alter the metabolism of APAP as assessed by either the extent of the covalent binding of APAP metabolites to hepatic macromolecules or by the depletion of hepatic reduced gultathione but completely abolished the induction of hepatic lipid peroxidation by APAP.
The present results demonstrate a participation of an acute oxidative stress in the mechanism of the induction of the liver cell necrosis by APAP.

PROTECTIVE EFFECT OF SUPEROXIDE DISMUTASE AGAINST Tert-BUTYLHYDROPEROXIDE CYTOTOXICITY IN CULTURED RAT HEPATOCYTES
Nakae Dai; Yoshiji Hitoshi; Kinugasa Tetsuo; Shiraiwa Kazumi; Konishi Yoichi
J Toxicol Pathol, 1990
The mechanisms by which human recombinant Cu-Zn superoxide dismutase prevents cultured rat hepatocytes from tert-butylhydroperoxide (TBHP) cytotoxicity were investigated. Both liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) and free (not liposome-encapsulated) human recombinant Cu-Zn superoxide dismutase (FSOD) were uptaken by cultured rat hepatocytes and prevented TBHP-induced cell killing dose-dependently. The 50%-effective final concentrations of FSOD for its cytoprotection and cellular internalization were approximately 9-and 6-fold higher than those of LSOD, respectively. Whereas the pretreatment of cultured rat hepatocytes with each of 5 different blockers of the endocytosis abolished both cellular uptake and cytoprotection of FSOD, the same treatment did not affect those of LSOD. The present results indicate that LSOD prevents TBHP-induced killing of cultured rat hepatocytes more efficiently than dose FSOD and suggest that the endocytosis-independent mechanism by which cultured rat hepatocytes uptake LSOD participates in the cytoprotection of such an enzyme.

RISK EVALUATION OF ACETAMINOPHEN IN PRE-EXISTING FATTY LIVER INDUCED BY CHOLINE-DEVOID DIET ON LIVER CARCINOGENESIS IN MALE F344 RATS
Takashima Yoshiharu; Maruyama Hiroshi; Kitazawa Shunji; Nakae Dai; Tsutsumi Masahiro; Denda Ayumi; Konishi Yoichi
J Toxicol Pathol, 1990
The initiating potential of acetaminophen (APAP) was investigated in prexisting fatty liver induced by choline-devoid (CD) diet in male F344 rats. APAP was intragastrically administered at the single necrogenic doses, 0.5g/kg, 1.0g/kg, 1.5g/kg body weight, Diethylnitrosamine (DEN) at 20mg/kg body weight was intraperitoneally injected after 4 weeks feeding of CD or choline-supplemented diet. In the CD treated animals, DEN significantly increased the number and area of both glutathione Stransferase placental form (GST-P) and γ-glutamyl transferase (GGT) -positive foci and nodules but APAP did not enhance at all. These results indicate that APAP does not possess significant initiating activity in damaged liver of rats.

Influence of Timing of Administration of Liposome‐encapsulated Superoxide Dismutase on Its Prevention of Acetaminophen‐induced Liver Cell Necrosis in Rats
Dai Nakae; Hitoshi Yoshiji; Kazuhiko Yamamoto; Hiroshi Maruyama; Tetsuo Kinugasa; Yoshinori Takashima; Ayumi Denda; Yoichi Konishi
Pathology International, 1990, [Reviewed]

ENHANCED LIVER METASTATIC POTENTIAL OF ALPHA-FETOPROTEIN-PRODUCING HUMAN GASTRIC-CARCINOMA AFTER CARBON TETRACHLORIDE-INDUCED LIVER-DAMAGE IN NUDE-MICE
H SAWADA; K NAKATANI; N MIYAGI; T NISHIWADA; A WATANABE; T OKUMURA; Y YAMADA; M TSUTSUMI; D NAKAE; H NAKANO; Y KONISHI
JAPANESE JOURNAL OF CANCER RESEARCH, Apr. 1989, [Reviewed]

PEROXIDATION-DEPENDENT AND PEROXIDATION-INDEPENDENT MECHANISMS BY WHICH ACETAMINOPHEN KILLS CULTURED RAT HEPATOCYTES
JL FARBER; TB LEONARD; ME KYLE; D NAKAE; A SERRONI; SA ROGERS
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, Dec. 1988, [Reviewed]

PREVENTIVE EFFECT OF 3-AMINOBENZAMIDE ON THE REDUCTION OF NAD LEVELS IN RAT-LIVER FOLLOWING ADMINISTRATION OF DIETHYLNITROSAMINE
K UCHIDA; S TAKAHASHI; K FUJIWARA; K UEDA; D NAKAE; Y EMI; M TSUTSUMI; K SHIRAIWA; T OHNISHI; Y KONISHI
JAPANESE JOURNAL OF CANCER RESEARCH, Oct. 1988, [Reviewed]

SUPEROXIDE-DISMUTASE AND CATALASE PROTECT CULTURED-HEPATOCYTES FROM THE CYTO-TOXICITY OF ACETAMINOPHEN
ME KYLE; S MICCADEI; D NAKAE; JL FARBER
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Dec. 1987, [Reviewed]

STUDIES OF CARCINOGENICITY OF SODIUM-CHLORITE IN B6C3F1 MICE
Y YOKOSE; K UCHIDA; D NAKAE; K SHIRAIWA; K YAMAMOTO; Y KONISHI
ENVIRONMENTAL HEALTH PERSPECTIVES, Dec. 1987, [Reviewed]

Possible Model of Liver Carcinogenesis Using Inhibitors of NAD+ ADP Ribosyl Transferase in Rats
Yoichi Konishi; Sehchi Takahashi; Dai Nakae; Kazuhiko Uchida; Masahiro Tsutsumi; Kazumi Shiraiwa; Ayumi Denda
Toxicologic Pathology, 1986, [Reviewed]

A Case Of Focal Nodular Hyperplasia Of The Liver In A 3 Year-Old Girl
Takashi Yoshikawa; Yasutoshi Fukai; Takahisa Sakurai; Masao Kikukawa; Hideaki Yoshida; Tuneo Shiratori; Yoshihiro Shimano; Yutaka Kinoshita; Hajime öishi; Seiichi Takahashi; Yoko Emi; Dai Nakae; Yoichi Konishi
Kanzo, 1984, [Reviewed]

Carcinogenic effects of 3-di(hydroxymethyl)-amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine in the small intestine of Ishibashi and Wistar rats
M. Takahashi; S. Nagase; S. Takahashi; Y. Emi; D. Nakae; K. Uchida; Y. Konishi
Experimental Pathology, 1984, [Reviewed]

CARCINOGENIC EFFECTS OF 3-DI(HYDROXYMETHYL)-AMINO-6-(5-NITRO-2-FURYLETHENYL)-1,2,4-TRIAZINE IN THE SMALL-INTESTINE OF ISHIBASHI AND WISTAR RATS
M TAKAHASHI; S NAGASE; S TAKAHASHI; Y EMI; D NAKAE; K UCHIDA; Y KONISHI
EXPERIMENTAL PATHOLOGY, 1984, [Reviewed]

ENHANCEMENT OF DEN INITIATION OF LIVER CARCINOGENESIS BY INHIBITORS OF NAD+ ADP RIBOSYL TRANSFERASE IN RATS
S TAKAHASHI; D NAKAE; Y YOKOSE; Y EMI; A DENDA; S MIKAMI; T OHNISHI; Y KONISHI
CARCINOGENESIS, 1984, [Reviewed]

Distribution and metabolism of N-nitrosobis(2-hydroxypropyl)amine in rats.
Mori Y; Takahashi H; Yamazaki H; Toyoshi K; Obara T; Makino T; Nakae D; Takahashi S; Konishi Y
IARC scientific publications, 1984, [Reviewed]

Hepatocarcinogenesis associated with NASH in mice fed a CDAA-HF-T(-) and the involvement of the signal factors
Noriko Kemuriyama; Akari Abe; Megumi Yuki; Kinuko Uno; Sae Nakane; Katsuhiro Miyajima; Dai Nakae
CANCER SCIENCE, Feb. 2022

A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a cholinedeficient, methionine-lowered, L-amino acid-defined, high-fat diet (vol 19, 251, 2020)
Noriko Suzuki-Kemuriyama; Akari Abe; Kinuko Uno; Shuji Ogawa; Atsushi Watanabe; Ryuhei Sano; Megumi Yuki; Katsuhiro Miyajima; Dai Nakae
LIPIDS IN HEALTH AND DISEASE, Jan. 2022

Effect of high fat diet on liver in db/db and KK-Ay mice　　　　　　　　　　　　　　　
Mandai K; Miyajima K; Kitamura S; Yamaguchi A; Uno K; Kuroki F; Nishida M; Shirasaka K; Tsustui T; Muro Y; Sugimoto M; Kemuriyama H; Shinohara M; Sasase T; Ohta T; Nakae D
Jul. 2021

2型糖尿病モデルdb/dbおよびKK-Ayマウスの腎臓における高脂肪食摂餌の影響　　　　　　　　　　　　　　　
山口彩音; 美谷島克宏; 宇野絹子; 杉本実紀; 黒木楓子; 西田芽衣; 小郷智記; 煙山紀子; 篠原雅巳; 中江大; 太田毅
The Journal of Toxicological Sciences, Jun. 2020

Development of an animal hepatocarcinogenesis model through non-obese (Asian-type) nonalcoholic steatohepatitis (NASH)
Noriko Kemuriyama; Satomi Uchino; Syunta Sato; Haruka Funamizu; Linfeng Gao; Kanjiro Ryuu; Kinuko Uno; Soon Hui Teoh; Syuuji Ogawa; Atsushi Watanabe; Katsuhiro Miyajima; Dai Nakae
CANCER SCIENCE, Dec. 2018

A mouse model of nonalcoholic steatohepatitis using a choline-deficient, methionine-lowered, L-amino acid-defined diet
Noriko Kemuriyama; Kaori Ikehata; Takuya Yamashita; Kinuko Uno; Soon Hui Teoh; Shuji Ogawa; Atsushi Watanabe; Katsuhiro Miyajima; Dai Nakae
CANCER SCIENCE, Jan. 2018

Responses to the standard for exchange of nonclinical data (SEND) in non-US countries
Takayuki Anzai; Masamichi Kaminishi; Keizo Sato; Laura Kaufman; Hijiri Iwata; Dai Nakae
Journal of Toxicologic Pathology, 01 Apr. 2015, [Reviewed]
Corresponding, Japanese Society of Toxicologic Pathology

Nitric oxide and cancer development
Robert A. Floyd; Yashige Kotake; Rheal A. Towner; We-Xing Guo; Dai Nakae; Yoichi Konishi
Journal of Toxicologic Pathology, 02 Jul. 2007, [Reviewed]

Antioxidant and signal-normalizing properties of phenyl N-tert-butyl nitrone and its derivatives in chemoprevention of hepatocellular carcinoma
D. Nakae; R. A. Floyd
CHEMICO-BIOLOGICAL INTERACTIONS, Jul. 2006
Lead

コリン欠乏アミノ酸(CDAA)食によるマウス肝発がんに対するOgg1遺伝子欠損の修飾効果
2006

S-nitrosylation in the development of choline deficiency-induced hepatocellular carcinoma
WX Guo; RH Broyles; R Towner; K Hensley; D Nakae; Y Kotake; RA Floyd
FREE RADICAL BIOLOGY AND MEDICINE, 2005

Role of nitric oxide in hepatocellular carcinoma development
RA Floyd; R Towner; WX Guo; K Hensley; RH Broyles; D Nakae; Y Kotake
FREE RADICAL BIOLOGY AND MEDICINE, 2005, [Reviewed]

O-11 Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats by increase of cytochrome P450 activities and modulation of estrogen metabolism in the liver(CARCINOGENICITY)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st Annual Meeting)
YOSHIDA Midori; NAKAE Dai; MAEKAWA Akihiko
Journal of toxicological sciences, 29 Oct. 2004
The Japanese Society of Toxicology

Existence of a threshold for induction of aberrant crypt foci in the rat colon with low doses of 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine
S. Fukushima; H. Wanibuchi; K. Morimura; S. Iwai; D. Nakae; H. Kishida; H. Tsuda; N. Uehara; K. Imaida; T. Shirai; M. Tatematsu; T. Tsukamoto; M. Hirose; F. Furukawa
Toxicological Sciences, Jul. 2004, [Reviewed]

Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats by increase of cytochrome P450 activities and modulation of estrogen metabolism in the liver
M Yoshida; D Nakae; A Maekawa
TOXICOLOGY AND APPLIED PHARMACOLOGY, Jun. 2004, [Reviewed]

Inhibitory effect of hydroxymatairesinol on the development of endometrial adenocarcinomas in rats
SI Katsuda; M Yoshida; N Saarinen; A Smeds; D Nakae; R Santti; A Maekawa
TOXICOLOGY AND APPLIED PHARMACOLOGY, Jun. 2004

Carcinogenic risks in the high-risk groups (SYMPOSIUM3: RECENT TOPICS ON THE RISK ASSESSMENT OF CHEMICAL CARCINOGENS) (Proceedings of the 30th Annual Meeting)
Nakae Dai; Takahashi Masakazu; Yoshida Midori; Uematsu Fumiyuki; Maekawa Akihiko
Journal of toxicological sciences, 31 Oct. 2003
The Japanese Society of Toxicology

Effect of neonatal exposure of high dose p-tert octylphenol on the ovary in rats (ENDOCRINE SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
Yoshida Midori; Katashima Sayumi; Maekawa Akihiko; Nakae Dai
Journal of toxicological sciences, 31 Oct. 2003
The Japanese Society of Toxicology

Narama, I., Imaida, K., Iwata, H., Nakae, D., Nishikawa, A., Harada, T.: A review of nomenclature and diagnostic criteria for proliferative lesions in the liver of rats by a working group of the Japanese Society of Toxicologic Pathology.
Isao Narama; Katsumi Imaida; Hijiri Iwata; Dai Nakae; Akiyoshi Nishikawa; Takanori Harada
J. Toxicol. Pathol., 2003

A flow cytometry study on nitric oxide and ROS formation in primary hepatocytes isolated from rats fed with an amino acid diet.
Y Kotake; H Kishida; D Nakae; RA Floyd
FREE RADICAL BIOLOGY AND MEDICINE, 2002

Dimethylarsinic acid induces 8-hydroxy-2 '-deoxyguanosine formation in the kidney of NCI-Black-Reiter rats
M Vijayaraghavan; H Wanibuchi; R Karim; S Yamamoto; C Masuda; D Nakae; Y Konishi; S Fukushima
CANCER LETTERS, Apr. 2001

Oncogene c-myc
T. Tsujiuchi; D. Nakae; Y. Konishi
Nippon rinsho. Japanese journal of clinical medicine, 2001

Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats
Yutaka Hatanaka; Dai Nakae; Mamoru Mutai; Kaoru Hashizume; Yuki Kamihara; Noriaki Kinoshita; Yoichi Tani; Gen-Ichi Danno; Shigeo Ohta; Yoichi Konishi; Hitoshi Ashida
Japanese Journal of Cancer Research, 2001

有機ヒ素化合物によるラット肝発癌促進作用　　　　　　　　　　　　　　　
鰐渕 英機; 西川 隆之; 魏 民; 木下 アンナ; 中江 大; 小西 陽一; 福島 昭治
日本病理学会会誌, Mar. 2000
(一社)日本病理学会

Age and organ dependent spontaneous generation of nuclear 8-hydroxydeoxyguanosine in male Fischer 344 rats
D Nakae; H Akai; H Kishida; O Kusuoka; M Tsutsumi; Y Konishi
LABORATORY INVESTIGATION, Feb. 2000

9.ラットにおけるコリン欠乏アミノ酸食による肝細胞死・再生・ 線維化より発癌に至る内因性機構の解析
25 Jan. 2000

Lack of promoting potential of dimethylarsinic acid in the kidney of male NCI-black reiter rats
Meenakshi Vijayaraghavan; Hideki Wanibuchi; Shinji Yamamoto; Katsuo Hakoi; Dai Nakae; Yoichi Konishi; Shoji Fukushima
Journal of Toxicologic Pathology, 2000
Japanese Society of Toxicologic Pathology

Endogenous liver carcinogenesis in the rat
D Nakae
PATHOLOGY INTERNATIONAL, Dec. 1999

Problem of study on carcinogenesis of experimental hepatoma.
Kanzo, 25 Feb. 1999
The Japan Society of Hepatology

Inhibition by phenyl N-tert-butyl nitrone of early phase hepato-carcinogenesis in rats fed a choline-deficient diet.
Y Kotake; D Nakae; K Kishida; KL Hensely; A Denda; Y Kobayashi; W Kitayama; T Tsujiuchi; H Sang; CA Stewart; T Tabatabie; RA Floyd; Y Konishi
FREE RADICAL BIOLOGY AND MEDICINE, 1998

Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: Association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver
H Wanibuchi; T Hori; Meenakshi, V; T Ichihara; S Yamamoto; Y Yano; S Otani; D Nakae; Y Konishi; S Fukushima
JAPANESE JOURNAL OF CANCER RESEARCH, Dec. 1997

Preventive effects of various antioxidants on endogenous liver carcinogenesis in rats fed a choline-deficient, L-amino acid-defined diet
NAKAE D.
Food Factors for Cancer Prevention, 1997

Effects of cell proliferation and cell death (apoptosis and necrosis) on the early stages of rat hepatocarcinogenesis
A Columbano; T Endoh; A Denda; O Noguchi; D Nakae; K Hasegawa; GM LeddaColumbano; AI Zedda; Y Konishi
CARCINOGENESIS, Mar. 1996

Dose-dependent induction of 8-hydroxyguanine and preneoplastic foci in rat liver by a food-derived carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, at low dose levels
T Kato; R Hasegawa; D Nakae; M Hirose; M Yaono; L Cui; Y Kobayashi; Y Konishi; N Ito; T Shirai
JAPANESE JOURNAL OF CANCER RESEARCH, Feb. 1996

A CASE OF EARLY GASTRIC MALIGNANT-LYMPHOMA DIAGNOSED AND COMPLETELY RESECTED BY STRIP BIOPSY
Y MORIMOTO; S KURIYAMA; H YOSHIJI; M MATSUMOTO; K MASUI; T SAKAMOTO; H KOJIMA; M YOSHIKAWA; H FUKUI; D NAKAE; Y KONISHI; M UENO; H NAKANO; T TSUJII
JOURNAL OF GASTROENTEROLOGY, Apr. 1995

PRIMARY ANGIOSARCOMA OF THE HEART : AN AUTOPSY CASE REPORT WITH IMMUNOHISTOCHEMICAL OBSERVATIONS
Maruyama Hiroshi; Yokose Yoshihiko; Kobayashi Eisaku; Endo Takehiro; Tsujiuchi Toshifumi; Tsutsumi Masahiro; Nakae Dai; Nishimine Kiyoshi; Kitamura Soichiro; Konishi Yoichi
28 Feb. 1995

Effects of oxidative stress induced by redox-enzyme modulation on rat hepatocarcinogenesis
Ayumi Denda; Takehiro Endoh; Dai Nakae; Yoichi Konishi
Toxicology Letters, 1995

ENHANCEMENT BY ORGANOSULFUR COMPOUNDS FROM GARLIC AND ONIONS OF DIETHYLNITROSAMINE-INDUCED GLUTATHIONE-S-TRANSFERASE POSITIVE FOCI IN THE RAT-LIVER
N TAKADA; T MATSUDA; T OTOSHI; Y YANO; S OTANI; T HASEGAWA; D NAKAE; Y KONISHI; S FUKUSHIMA
CANCER RESEARCH, Jun. 1994

SPONTANEOUS PASSAGE OF A COLON CAST IN THE ABSENCE OF ABDOMINAL ANEURYSM
H YOSHIJI; D NAKAE; R SUGIYA; Y MIZUMOTO; M TSUTSUMI; K HIRIGUCHI; Y YOKOSE; R SAKURAI; H FUKUI; T TSUJII; Y KONISHI
JOURNAL OF GASTROENTEROLOGY, Feb. 1994

HIGH-INCIDENCE OF HEPATOCELLULAR CARCINOMAS INDUCED BY A CHOLINE-DEFICIENT L-AMINO-ACID DEFINED DIET IN RATS
D NAKAE; H YOSHIJI; Y MIZUMOTO; K HORIGUCHI; K SHIRAIWA; K TAMURA; A DENDA; Y KONISHI
CANCER RESEARCH, Sep. 1992

INHIBITORY EFFECT OF DIETARY IRON-DEFICIENCY ON INDUCTIONS OF PUTATIVE PRENEOPLASTIC LESIONS AS WELL AS 8-HYDROXYDEOXYGUANOSINE IN DNA AND LIPID-PEROXIDATION IN THE LIVERS OF RATS CAUSED BY EXPOSURE TO A CHOLINE-DEFICIENT L-AMINO-ACID DEFINED DIET
H YOSHIJI; D NAKAE; Y MIZUMOTO; K HORIGUCHI; K TAMURA; A DENDA; T TSUJII; Y KONISHI
CARCINOGENESIS, Jul. 1992

PRODUCTION OF BOTH 8-HYDROXYDEOXYGUANOSINE IN LIVER DNA AND GAMMA-GLUTAMYLTRANSFERASE-POSITIVE HEPATOCELLULAR LESIONS IN RATS GIVEN A CHOLINE-DEFICIENT, L-AMINO ACID-DEFINED DIET
D NAKAE; H YOSHIJI; H MARUYAMA; T KINUGASA; A DENDA; Y KONISHI
JAPANESE JOURNAL OF CANCER RESEARCH, Nov. 1990

ENDOCYTOSIS-INDEPENDENT UPTAKE OF LIPOSOME-ENCAPSULATED SUPEROXIDE-DISMUTASE PREVENTS THE KILLING OF CULTURED-HEPATOCYTES BY TERT-BUTYL HYDROPEROXIDE
D NAKAE; H YOSHIJI; T AMANUMA; T KINUGASA; JL FARBER; Y KONISHI
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, Jun. 1990

LACK OF HEPATOCARCINOGENIC POTENTIAL OF ACETAMINOPHEN IN RATS WITH LIVER-DAMAGE ASSOCIATED WITH A CHOLINE-DEVOID DIET
H MARUYAMA; Y TAKASHIMA; Y MURATA; D NAKAE; H EIMOTO; M TSUTSUMI; A DENDA; Y KONISHI
CARCINOGENESIS, Jun. 1990

酸化性ストレスによる病的現象発生とsuperoxide dismutase
23 Apr. 1988

PERSISTENT EFFECT OF A LOW-DOSE OF PREADMINISTERED DIETHYLNITROSAMINE ON THE INDUCTION OF ENZYME-ALTERED FOCI IN RAT-LIVER
S TAKAHASHI; M TSUTSUMI; D NAKAE; A DENDA; T KINUGASA; Y KONISHI
CARCINOGENESIS, Apr. 1987

ROLE OF POLY ADP-RIBOSYRATION REACTION ON THE INDUCTION OF GAMMA-GTP POSITIVE FOCI IN RAT-LIVER
S TAKAHASHI; K UCHIDA; D NAKAE; Y KONISHI; T OHNISHI
JOURNAL OF RADIATION RESEARCH, 1985

INVOLVEMENT OF POLY-ADP RIBOSYLATION IN THE INDUCTION OF HYPERPLASTIC NODULES IN RAT-LIVER INITIATED BY DIETHYLNITROSAMINE (DEN)
Y KONISHI; S TAKAHASHI; D NAKAE; K UCHIDA; H MARUYAMA; Y YOKOSE; Y EMI; T OBARA; T MAKINO; A DENDA
PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, 1984

図で見る公衆衛生学
Mar. 2017
9784865842227

図で見る公衆衛生学
Mar. 2015
9784865840254

Alternatives to animal experiments in the regulation of food, the Japanese situation　　　　　　　　　　　　　　　
Nakae, D.
ILSI 2021International Workshop for Non-animal Approaches in Food Sector, 21 Oct. 2021, [Invited]

がん研究の資材有効保存と利用に関する研究
2005 - 2009

Study on the Mechanisms Underlying Endogenous Hepatocarcinogenesis Induced Only by the Manipulation of Food Composition
Grant-in-Aid for Scientific Research (C)
Sasaki Institute, Sasaki Foundation
2004 - 2005
The present study assessed possible involvement of gene mutation in the early stage hepatocarcinogenesis, using gpt delta rats with a reporter transgene. In the study, 6-week-old male gpt delta rats originated from either Fischer 344 (F344) or Sprague-Dawley (SD) strains were used. Two rat hepatocarcinogenesis models were featured, an endogenous one with a choline-deficient L-amino acid-defined (CDAA) diet and an exogenous one with N-nitrosodiethylamine (DEN). Phenyl N-tert-butyl nitrone (PBN) was chosen as a negative modifier of hepatocarcinogenesis. The experiment was conducted by 15 groups each consisting of 6 animals (F344 for groups 1-8 and SD for groups 9-15). Groups 1, 2, 3 and 4 received the CDAA diet, CDAA+PBN (0.13% in drinking water), a choline-supplemented L-amino acid-defined (CSAA) diet and CSAA+PBN, respectively, from the end of week 2 for 16 weeks. Groups 5 and 6 received DEN of 2 weekly intraperitoneal doses of 100mg/kg body weight at the beginning. Only group 6 received PBN from the end of week 2 for 16 weeks. Groups 7 and 8 received vehicle in place of DEN and were similarly treated to groups 5 and 6, respectively. Groups 9-13, 14 and 15 were treated similarly to groups 1-5, 7 and 8, respectively. At the end of week 18, all animals were killed to obtain the liver for the examination for the development of preneoplastic lesion, oxidative DNA injury (8-oxoguanine, 8-oxoG) and gene mutation (gpt assay). In the endogenous model, the CDAA diet induced preneoplastic lesions only in F344. The 8-oxoG levels increased by the CDAA diet in both strains, F344 being higher than SD. The gene mutation increased by both the CDAA and CSAA diets with the same extent, only in F344. The CSAA diet predominantly caused GC/AT transition and deletion, while the CDAA diet caused those in association with GC/TA transversion, specific to 8-oxoG. PBN inhibited all changes caused by the CDAA diet but not gene mutation caused by the CSAA diet. In the exogenous model, DEN induced preneoplastic lesions more but smaller in F344 and more as well as larger in SD than the CDAA diet. The lesions were more in SD than in F344. The 8-oxoG levels increased by DEN in both strains, lower and higher than the CDAA case, respectively. The gene mutation increased by DEN, higher than the CDAA case, in both strains, higher in SD than in F344. PBN did not exert any influence on changes caused by DEN. These results indicate that the gene mutation is involved in both endogenous and exogenous rat hepatocarcinogenesis at its early stage but in different manners, and plays roles in the mechanisms underlying the strain difference.

Risk Assessment of Carcinogenesis due to Environmental Agents
Grant-in-Aid for Scientific Research on Priority Areas
Osaka City University Medical School
1996 - 1999
1) It was strongly suggested that a no observed effect level exists for rat liver carcinogenicity of diethylnitrosamine. 2) SCID mice proved useful for detection of 2-amino-3-methylimidazo [4,5-f] quinoline-low dose carcinogenicity. 3) Phenobarbital treatment to rats induced P450 and hydroxyradicals in the liver, resulting in increase of 8-hydroxyguanine (8-OHG) formation. 4) Further studies are required risk assessment for carcinogenesis using transgenic or knockout mice. 5) PLACE-SSCP method was examined to confirm the utility of detection for rare mutations of oncogenes or tumor suppressor genes related to cancer induction. 6) Mesurement of 8-OHG is important for risk assessment of carcinogenesis in animals.

Basic Research on the Development and Progression of Pancreatic Duct Adenocarcinoma
Grant-in-Aid for Scientific Research (A)
Nara Medical University
1996 - 1999
The importance of basic research related to pancreatic cancer should be focused on ductal adenocarcinoma since the incidence of * cancer is the highest, showing poor prognosis among various histological types of human pancreatic malignant neoplasms. However, experimental pancreatic duct adenocarcinoma (PDA) resembled histologically, biologically and genetically to human PDA can be induced by nitrosamines only in hamsters and dogs but not in other animal spieces. In this projects, we performed the research related to control the development and progression of PDA using a rapid production model of PDC in hamsters which was developed by us (Mizumoto, K. et al.,J.Natl.Cancer Inst.1998 ; 80 : 1564-1567) and PDA cell lines which were also established by us (Mori, T.et al.Int.J.Pancreao.1994 ; 16 : 171-177).
Genetic alterations related to the development and progression of PDA
1. The shortened telomeas and increased telomerase activities were detected in hamster PDA and also increased telomerase activities were detected in 32 out of 38 cases (84%) of human PDA tissues. Among those cases, Ki-ras mutations were also detected in 20 cases (53%).
2. Midkine, one of growth factors, was overexpressed at mRNA level and also expressed at protein level in PDAs.
3. MMP-2, one of MMP families, was importantly involved in the development and progression of PDAs.
4. Bax, one of apoptosis related genes, was overexpressed in PDAs.
5.β-catenine was not involved in the development and progression of PDAs.
Possible control of PDA
1. Possible involvement of heterocyclic amines of Trp-p-1 and DiMeIQx in the development of PDA was suggested.
2. OPB-3206, a inhibition of MMPs, inhibited pancreatic duct carcinogenesis.
3.β-carotin at a dose of 0.0025%, palm carotin at 0.004%, greentea polyphynol at 0.05 and 0.5%, 4-hydoxyphenyl retinamide (4-HPR) at 0.0015% and tranexamic acid at 0.1% in the diets inhibited pancreatic duct carcinogenesis.
4. 4-HPR at the concentration of 10μ M and auraptene at 50μ M introduced apoptosis in culture PDA cells.

ラット肝における酸化性DNA障害依存性発癌機構と肝細胞壊死
1992 - 1992