Tongue Carcinogenic Susceptibility of p53 Deficient Mice to Methyl-n-amylnitrosamine

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概要

• 論文の詳細を見る

• Mutation of the p53 tumor suppressor gene is a common genetic alteration in human squamous cell carcinoma of the tongue. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we investigated the susceptibility of p53 nullizygous (-/-), heterozygous (+/-), and wild type (+/+) mice to methyl-n-amylnitrosamine (MNAN) induced squamous cell carcinoma (SCC) of the tongue. The p53 (+/-), and (+/+) mice were treated with 5 p.p.m. MNAN in drinking water for 8 weeks then held without further treatment for an additional 7 or 17 weeks, and killed at 15 or 25 experimental weeks. A separate group of the p53 (-/-) mice were given 5 p.p.m. MNAN for 8 weeks and were killed at 15 weeks. At 15 weeks, SCCs and papillomas were observed in 5/12 (41.7%) and 2/12 (16.7%) of p53 (-/-) mice, respectively, but not in p53 (+/-) and (+/+) mice. At 25 weeks, carcinomas in situ (CIS) were detected in 1/16 (6.3%) of p53 (+/-) and 1/13 (7.7%) of p53 (+/+) mice, and a papilloma was observed in the p53 (+/-) mouse which had CIS. PCR-single strand conformation polymorphism analysis of exons 5-8 of the p53 gene demonstrated a missense mutation in the CIS from p53 (+/+) mouse. These results suggest that a lack of p53 gene function predisposes the tongue to the development of SCCs in mice treated with MNAN, and show that p53 (-/-) mouse was a useful model for demonstrating carcinogenicity of MNAN to tongue.

• 日本毒性病理学会の論文
• 2002-12-25

著者

• 今井 敏夫

  Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.

• Tsukamoto T

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• TSUKAMOTO Tetsuya

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• YAMAMOTO Masami

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• YANAI Tokuma

  Department of Veterinary Pathology, Gifu University

• MASEGI Toshiaki

  Department of Veterinary Pathology, Gifu University

• TATEMATSU Masae

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• SAKAI Hiroki

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• DONEHOWER Lawrence

  Department of Molecular Virology and Microbiology, Baylor College of Medicine

• IIDAKA Takeshi

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• SHIRAI Norimitsu

  Division of Oncological Pathology, Aichi Cancer Center Research Institute

• Iidaka Takeshi

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• 坂井 宏明

  帯広畜産大学畜産学部獣医学科家畜内科学教室

• Yanai T

  Department Of Veterinary Pathology Gifu University

• Totsuka Yukari

  大阪府立大学先端科学イノベーションセンター 遺伝子環境科学研究室

• Totsuka Y

  Cancer Prevention Basic Research Project

• Tatematsu Masae

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Tatematsu M

  愛知県がんセンター研究所 腫瘍病理学部

• Tsukamoto Tetsuya

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Yanai Tokuma

  Department Of Veterinary Pathology Faculty Of Agriculture Gifu University

• Yamachika Takasuke

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Imai Toshio

  Laboratory Of Pathology Aichi Cancer Center Research Institute

• Takaoka Masaya

  Medicinal Safety Research Laboratories Daiichi-sankyo Co. Ltd.

• Shirai Norimitsu

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Tsukamoto Takahisa

  First Department Of Oral And Maxillofacial Surgery School Of Dentistry

• Yamamoto M

  Aichi Cancer Center Research Institute

• Tsukamoto Takahisa

  Division Of Oncological Pathology Aichi Cancer Center Research Institute

• Donehower Lawrence

  Department Of Molecular Virology And Microbiology Baylor College Of Medicine

• Masegi Toshiaki

  Department Of Veterinary Pathology Faculty Of Agriculture Gifu University

• Tsukamoto T

  Department Of Public Health Osaka City University Graduate School Of Medicine

• Totsuka Yukari

  国立がん研究センター研究所 発がんシステム研究分野

• Masegi Toshiaki

  Department Of Gastroenterology And Metabolism Nagoya City University Graduate School Of Medical Scie

• Makita Takashi

  Medicinal Safety Research Laboratories Daiichi Sankyo Co. Ltd.:department Of Veterinary Pathology Gr

• Imai T

  Human Genome Ctr.

• YANAI Tokuma

  Department of Pathogenetic Veterinary Sciences, United Graduate School of Veterinary Sciences, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan

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