API PUBL 32-32406-1985
评估 RO-1 81-15 和 PS8-76D5-SAT 在体外肝细胞 DNA 修复试验中诱导计划外 DNA 合成的潜力

EVALUATION OF THE POTENTIAL OF RO-1@ 81-15@ AND PS8-76D5-SAT TO INDUCE UNSCHEDULED DNA SYNTHESIS IN THE IN VIVO-IN VITRO HEPATOCYTE DNA REPAIR ASSAY

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标准号

API PUBL 32-32406-1985

发布

1985年

发布单位

API - American Petroleum Institute

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API PUBL 32-32406-1985

 

 

适用范围

INTRODUCTION The measurement of chemically Induced DNA repair as unscheduled DNA synthesis (UDS) has been shown to be an excellent predictor of genotoxic and carcinogenic potential. A number of in vitro assays for measurement of UDS have been described that employ a variety of cell lines (Trosko and Yager@ 1974; San and Stich@ 1975; Martin et al.@ 1978)@ Including primary cultures of rat hepatocytes (Williams@ 1977). This latter assay offers the advantage of using a target cell that is metabolically competent. Still@ these systems often do not reflect the true genotoxicity present in the whole animal@ and even the in vitro hepatocyte DNA repair assay has been shown to be unresponsive to some classes of compounds@ such as nitroaromatlcs (Bermudez et al.@ 1979; Probs et al.@ 1981). The in vivo-ln vitro hepatocyte DNA repair assay (Mirsalis and Butterworth@ 1980) Involves treatment of animals rather than cells in culture and has been shown to be responsive to a wide variety of genotoxic agents@ Including nitroaromatlcs (Mirsalis et al.@ 1982a). In an in vivo system@ factors related to uptake@ metabolic activation@ distribution@ detoxification@ and elimination are inherently accounted for. This assay has been demonstrated to be useful in the study of sex differences. effects of chronic exposure (Mirsalis and Butterworth@ 1982)@ and the role of activation of compounds by intestinal microflora (Mirsalis et al.@ 1982a). In particular@ this assay Is extremely useful for the detection and study of genotoxic hepatocarclnogens (Mirsalis et al.@ 1982b).

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