API PUBL 33-31826-1986
评估 PS-8-76D5-ARO 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 PS-8-76D5-ARO TO INDUCE UNSCHEDULED DNA SYNTHESIS IN THE IN VIVO-IN-VITRO HEPATOCYTE DNA REPAIR ASSAY


 

 

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标准号
API PUBL 33-31826-1986
发布
1986年
发布单位
API - American Petroleum Institute
当前最新
API PUBL 33-31826-1986
 
 
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; Hartin 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 nitroaromatics (Bermudez et al.@ 1979; Probst et al.@ 1981). The in vivo-in 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 nitroaromatics (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 (Kirsalis et al.@ 1982a). In particular@ this assay is extremely useful for the detection and study of genotoxlc hepatocarcinogens (Mirsalis et al.@ 1982b).

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