Effect of pretreatment with hepatic mixed-function oxidase inducers on the genotoxicity of four 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). 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.
Shaddock
J G
JG
Food and Drug Administration, Division of Genetic Toxicology, Jefferson, AR 72079.
Robinson
B Y
BY
Casciano
D A
DA
D000179:Acrylates / Q000633:toxicity; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009154:Mutation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000633:toxicity; D017905:Phosphites; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity; D015039:Ziram / Q000633:toxicity
D000179:Acrylates; D001140:Aroclors; D002273:Carcinogens; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017905:Phosphites; D014051:Toluene 2,4-Diisocyanate; D008748:Methylcholanthrene; D015039:Ziram; C026942:2,6-diisocyanatotoluene; D011078:Polychlorinated Biphenyls; C100245:bromebric acid; C047356:dimethyl hydrogen phosphite