API PUBL 33-31826-1986 EVALUATION OF THE POTENTIAL OF PS-8-76D5-ARO TO INDUCE UNSCHEDULED DNA SYNTHESIS IN THE IN VIVO-IN-VITRO HEPATOCYTE DNA REPAIR ASSAY
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).
API PUBL 33-31826-1986 history
1986API PUBL 33-31826-1986 EVALUATION OF THE POTENTIAL OF PS-8-76D5-ARO TO INDUCE UNSCHEDULED DNA SYNTHESIS IN THE IN VIVO-IN-VITRO HEPATOCYTE DNA REPAIR ASSAY