bromebric-acid and 2-6-diisocyanatotoluene

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). Cytembena 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.

Topics: Acrylates; Animals; Aroclors; Carcinogens; Cells, Cultured; DNA Repair; Dose-Response Relationship, Drug; Isomerism; Liver; Male; Methylcholanthrene; Mutagenicity Tests; Mutation; Organophosphonates; Organophosphorus Compounds; Phosphites; Polychlorinated Biphenyls; Rats; Rats, Inbred F344; Toluene 2,4-Diisocyanate; Ziram