染色体異常を指標としたがん原性物質検出法の開発と評価
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概要
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The Chromosomal Aberration Test using cultured mammalian cells, was proposed as an alternative screening tool to bacterial mutation assays(Ames test), for the detection of environmental mutagens and/or carcinogens. The Micronucleus Test in mice was also proposed as an additional in vivo test for evaluating the genotoxic potential of those chemicals which were positive in the in vitro systems. Mutagenic potency in the Ames test was estimated from the number of revertant colonies induced per unit dose(mg/plate)and in the Chromosomal Aberration Test was calculated from the minimum dose(mg/ml)inducing at least 20% aberrant cells(D_<20> value). It was found from these assays that there were some 10^6 fold differences in their mutagenic/clastogenic potencies and that only potent chemicals may give positive responses in the in vivo Micronucleus Test. It was also found that, in the Chromosome Aberration Test, the incidence of exchange-type rather than break-type aberrations is more important in predicting the carcinogenic risk of exposure to clastogens. In this review, the significance of a battery system comprising at least three different mutagenicity tests is discussed together with the importance of quantitative rather than qualitative evaluation in the genotoxicity of chemicals. In addition, recent analytical studies on the mechanisms of induced chromosomal aberrations in cultured cells, using the Fluorescence In Situ Hybridization(FISH)technique and Laser Scan Cytometry(LSC)are presented.
- 1998-07-21
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