In vivo Approaches to Study Mechanism of Action of Genotoxic Carcinogens
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概要
- 論文の詳細を見る
Genotoxic carcinogens are chemicals or factors which not only induce neoplastic lesions in animal bioassays but also test positive in genotoxicity assays in vitro or in vivo. However, it is actually difficult to discriminate genotoxic and non-genotoxic carcinogens because both assays are basically independent each other, which raises a simple query as to how much the detected genotoxic potential can consequently contribute to carcinogenicity. To clarify this critical issue, we have studied the mechanisms of action of carcinogens in transgenic rats or mice carrying reporter genes, which are expected as powerful tools for the simultaneous evaluation of both genotoxicity and carcinogenicity at the same organ level. A number of studies of genotoxic carcinogens using these transgenic rodents have revealed good correlations between genotoxicity and carcinogenicity in terms of mechanism of action. On the other hand, a known non-genotoxic carcinogen dicyclanil increased in vivo genotoxicity as well as oxidative DNA damage in female mice, consistently with the sex specificity of its carcinogenicity, albeit without clear evidence of direct DNA reactivity. In contrast, a genotoxic chlorinated water by-product MX failed to exert in vivo genotoxicity and carcinogenicity in mice. We also confirmed that such reporter gene-carrying rodents are not susceptible or resistant to carcinogenicity as compared with intact counterparts. These results thus indicate that understanding of the detailed mechanism of carcinogenic action could be crucial for more precise risk assessment, and bioassay systems using transgenic rodents carrying reporter genes would be extremely useful for that purpose.
- 日本環境変異原学会の論文
- 2008-11-20
著者
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Umemura T
Division Of Pathology National Institute Of Health Sciences
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MASUMURA Kenichi
Division of Genetics and Mutagenesis, National Institute of Health Sciences
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Nishikawa Akiyoshi
Division of Pathology, National Institute of Health Sciences
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Mitsumori Kunitoshi
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Mitsumori Kunitoshi
東京大学医科学研究所 癌細胞シグナル分野
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Mitsumori Kunitoshi
国立医薬品食品衛生研究所 病理部
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OKAMURA Toshiya
Division of Pathology, National Institute of Health Sciences
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ISHII Yuji
Division of Pathology, National Institute of Health Sciences
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UMEMURA Takashi
Division of Pathology, National Institute of Health Sciences
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TASAKI Masako
Division of Pathology, National Institute of Health Sciences
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NOHMI Takehiko
Division of Genetics and Mutagenesis, National Institute of Health Sciences
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Nishimura T
Division Of Environmental Chemistry
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Mitsumori K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Tasaki Masako
Division Of Pathology National Institute Of Health Sciences
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三森 国敏
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Inoue Tomoki
Division of Pathology, National Institute of Health Sciences
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Okamura Toshiya
Division Of Pathology National Institute Of Health Sciences
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Ishii Yuji
Division Of Pathology National Institute Of Health Sciences
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Maita K
The Institute Of Environmental Toxicology:agrotox Inc.
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Mitsumori Kunitoshi
Department Of Pathology National Institute Of Health Sciences
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Inoue Tomoki
Division Of Pathology National Institute Of Health Sciences
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Nishikawa A
Div. Of Pathology National Inst. Of Health Sciences
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Nishikawa Akiyoshi
Division Of Pathology Biology Safety Research Center National Institute Of Health Sciences
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Nishikawa A
National Inst. Health Sci. Tokyo Jpn
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Nishikawa A
National Institute Of Health Science Osaka Branch National Institute Of Health Sciences
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Umemura Takashi
Division Of Pathology National Institute Of Health Sciences
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Masumura Kenichi
Division Of Genetics And Mutagenesis National Institute Of Health Sciences
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Unno Takashi
Division Of Pathology National Institute Of Health Sciences
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Umemura T
Hokkaido Univ. Sapporo Jpn
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Umemura Takashi
Division Of Pathology National Institute Of Health Science
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Matsumoto K
Drug Safety Research Laboratories Pharmaceutical Research Division Takeda Chemical Industries Ltd.:l
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三森 国敏
Division Of Pathology National Institute Of Health Sciences
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Unno Takashi
Japan Pharmaceutical Manufactures Association (jpma):kanebo Ltd
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Nohmi Takehiko
Division Of Genetics And Mutagenesis National Institute Of Health Sciences
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Matsumoto K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Masegi Toshiaki
Department Of Veterinary Pathology Faculty Of Agriculture Gifu University
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Umemura Takashi
Laboratory Of Comparative Pathology Graduate School Of Veterinary Medicine Hokkaido University
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Ishii Yuji
Division Of Pathology National Institute Of Health Science
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