EFFECT OF PRETREATMENT WITH HEPATIC MIXED-FUNCTION OXIDASE INDUCERS ON THE GENOTOXICITY OF 4 RAT CARCINOGENS IN THE HEPATOCYTE DNA-REPAIR ASSAY

Four genotoxic rat carcinogens, previously reported as negative in the standard hepatocyte/DNA repair assay, were studied in hepatocyte cultures derived from the livers of rats pretreated with the hepatic mixed-function oxidase (MFO) inducers, Aroclor (ARO) and 3-methylcholanthrene (3-MC). Cyternbena and dimethyl hydrogen phosphite induced positive dose-dependent DNA repair responses in ARO and 3-MC-pretreated cultures, while 2, 4-, 2, 6-toluene diisocyanate, and ziram were negative for unscheduled DNA synthesis in cultures from both pretreatments. The results from this study indicate that pretreatment with hepatic MFO inducers lowers the false-negative detection rate of various genotoxic rat carcinogens and other organ-specific genotoxins and significantly increases the sensitivity of the in vitro rat hepatocyte/DNA repair assay. © 1990 Oxford University Press.