Induction of unscheduled DNA synthesis in rat and hamster hepatocytes by cooked food mutagens.

The genotoxicity of the cooked-food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was studied by monitoring the induction of DNA repair (unscheduled DNA synthesis; UDS) in primary cultures of rodent hepatocytes. The hepatocytes were derived from male Sprague-Dawley rats or Syrian hamsters by collagenase perfusion and the cells were cultured for 4 hr before being exposed to various concentrations of the mutagens. DNA repair was determined by measuring incorporation of [3H]thymidine into extracted DNA over 17 hr using beta-scintillation counting. Dose-related increases in UDS were clearly seen in hamster hepatocytes treated with MeIQ, IQ and the positive control 2-acetylaminofluorene (AAF), and a weak response was induced by MeIQx and Trp-P-1. In the rat hepatocytes only MeIQ and AAF gave clear positive responses. Furthermore it was noted that all the mutagens displayed a more pronounced UDS response in hamster hepatocytes than in rat cells. Studies of the activation of MeIQ by hepatocytes to a bacterial mutagen suggest that this difference is probably a consequence of the greater capacity of hamster cells to activate the mutagens to genotoxic metabolites.