In vivo Approaches to Study Mechanism of Action of Genotoxic Carcinogens
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- Nishikawa Akiyoshi
- 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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- Ishii Yuji
- 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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- Okamura Toshiya
- Division 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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- Masumura Kenichi
- Division of Genetics & Mutagenesis, National Institute of Health Sciences
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- Nohmi Takehiko
- Division of Genetics & Mutagenesis, National Institute of Health Sciences
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Abstract
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.<br>
Journal
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- Genes and Environment
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Genes and Environment 30 (4), 120-124, 2008
The Japanese Environmental Mutagen Society
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Details 詳細情報について
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- CRID
- 1390282680233639808
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- NII Article ID
- 110007007985
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- NII Book ID
- AA1212552X
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- COI
- 1:CAS:528:DC%2BD1MXitlCns7Y%3D
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- ISSN
- 18807062
- 18807046
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- NDL BIB ID
- 9741242
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed