α-Naphthylisothiocyanate Induces Intrahepatic Bile Duct with Greater Proliferation in Female Rats than in Males

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概要

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• The present study was conducted with the original purpose of investigating the possibility that α-naphthylisothiocyanate (ANIT) might induce intrahepatic cholangiocellular neoplasms in rats after appropriate carcinogenesis-initiating treatments, based on its known effect of causing intrahepatic bile duct proliferation. Fischer 344 rats (6 weeks old) were given 3 weekly intraperitoneal administrations of vehicle (female and male), N-nitrosobis(2-oxopropyl)amine (BOP) (20 mg/kg body weight, female and male) or N-nitrosodimethylamine (DMN) (10 mg/kg body weight, male only), and fed a basal diet with or without 200 ppm of ANIT from the commencement for up to 24 weeks. Animals were sequentially sacrificed at the ends of weeks 8, 16 and 24 to examine morphological changes in the liver. ANIT caused proliferation of intrahepatic bile duct epithelial cells with no atypia when administered alone or in combination with BOP (female and male) or DMN (male only), while neither BOP nor DMN caused bile duct proliferation per se or altered the magnitude of the effect of ANIT. The degree of bile duct proliferation caused by ANIT was greater in females than in males. No hepatocellular or liver (pre)neoplastic changes were observed. These results indicate that although ANIT does not induce any neoplastic changes in the liver even after initiation with BOP (female and male) or DMN (male), it causes non-neoplastic intrahepatic bile duct proliferation with a clear sex difference.

• 2004-09-30

著者

• WATANABE Naoto

  Department of Radiology, Toyama Medical and Pharmaceutical University

• NAKAE Dai

  Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health

• Nakae Dai

  東京都健康安全研究センター

• Nakae Dai

  Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health:toky

• Nakae Dai

  Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health

• MAEKAWA Akihiko

  Chemical Management Center, National Institute of Technology and Evaluation

• Yoshida Midori

  National Institute of Health Sciences

• UEMATSU Fumiyuki

  Department of Pathology, Sasaki Institute

• YOSHIDA Midori

  Department of Pathology, Sasaki Institute

• TAKAHASHI Masakazu

  Department of Pathology, Sasaki Institute

• ABE Masayoshi

  Department of Pathology, Sasaki Institute

• IGARASHI Maki

  Department of Pathology, Sasaki Institute

• SUZUKI Noriko

  Department of Pathology, Sasaki Institute

• MAEKAWA Akihiko

  Director, Sasaki Institute

• Watanabe Naoto

  Department Of Pathology Sasaki Institute

• Yoshida Midori

  Div. Of Pathology National Inst. Of Health Sciences

• Yoshida Midori

  Department Of Pathology Sasaki Institute

• Igarashi Maki

  Laboratory Of Protection Of Body Function Department Of Food And Nutritional Science Graduate School

• Abe Masayoshi

  Department Of Pathology Sasaki Institute

• Abe Masayoshi

  Department Of Biology Faculty Of Science Shizuoka University

• Abe Masayoshi

  Biological Research Laboratories, Nissan Chemical Industries, Ltd.

• Maekawa A

  Chemical Management Center National Inst. Of Technol. And Evaluation

• Maekawa Akihiko

  Chemical Management Center National Institute Of Technology And Evaluation

• Maekawa Akihiko

  Safety Assessment Division Chemical Management Center National Institute Of Technology And Evaluatio

• Abe Masayoshi

  Biological Research Laboratories Nissan Chemical Industries Ltd.

• Takahashi Masakazu

  Division Of Pathology National Institute Of Health Sciences

• Takahashi Masakazu

  Department Of Microbiology Niigata College Of Pharmacy

• Uematsu Fumiyuki

  Department Of Pathology Sasaki Institute Sasaki Foundation

• Watanabe Naoto

  Department Of Anesthesia Social Insurance Sagamino Hospital

• Nakae Dai

  Department Of Pathology Sasaki Institute

• Suzuki Noriko

  Department Of Biochemistry And Molecular Biology Division Of Gene Therapy Research Center For Advanc

• Takahashi Miwa

  National Institute of Health Sciences

• Suzuki Noriko

  Department Of Clinical And Molecular Endocrinology Tokyo Medical And Dental University Graduate Scho

• Takahashi Masakazu

  Department Of Pathology Sasaki Institute Sasaki Foundation

• Takahashi Masakazu

  National Institute Of Health Sciences

• Takahashi Masakazu

  Department Of Food Science And Technology Faculty Of Agriculture Kyoto University

• Takahashi Masakazu

  Department Of Bioscience Faculty Of Biotechnology Fukui Prefectural University

• Suzuki Noriko

  Department of Applied Pharmacology, Kyoto Pharmaceutical University

• IGARASHI Maki

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development

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