Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2148518 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2010 | 6 Pages |
Abstract
A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
Keywords
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Authors
Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi Imamura, Atsushi Miyazaki, Masayoshi Kawabata, Shigenori Minowa, Akihisa Maeda, Makoto Hayashi,