Induction of DNA damage and repair synthesis in freshly isolated rat hepatocytes by the proallatocidin precocene II.

The proallatocidin precocene II (6,7-dimethoxy-2,2-dimethyl-2H-benzo-[b]pyran) has previously been shown to induce centrolobular liver necrosis. Here we have examined the ability of precocene II to produce DNA damage in suspensions of freshly isolated rat hepatocytes using the alkaline elution technique with N-methyl-N'-nitro-N-nitrosoguanidine as a positive control. At concentrations (10(-4)-10(-5) M) which did not induce cytotoxicity as judged by the leakage of glutamic-oxaloacetic transaminase, precocene II was capable of producing DNA single-strand breaks. In addition, a dose-dependent DNA repair synthesis (unscheduled DNA synthesis, UDS) was detected in hepatocytes exposed to precocene II. The induction of UDS was measured by incorporation of [3H]thymidine into purified hepatic DNA via a membrane filter retention method and liquid scintillation counting. Hence, results obtained in the present study indicate the potential genotoxicity of precocene II and the utility of DNA damage and repair assays in genetic toxicology.