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Cumulative effects of chromosome aberrations and sister chromatid exchanges (SCEs) were studied in hepatocytes of F344 rats exposed in vivo to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day. Hepatocytes were isolated 24 h after 1, 7, 14 or 28 repeated doses (once a day) by gastric intubation and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 h. Multiple treatment with IQ or nitro-IQ induced significant chromosome aberrations time- and dose-dependently, the maximum frequency of chromosome aberrations in metaphase cells being 39 and 33% respectively, while that in controls was 1.1%. Single treatment with IQ or nitro-IQ induced significant SCEs dose-dependently, the maximum frequency being 0.83 and 0.79 per chromosome respectively, while the control value was 0.51. Multiple treatment with nitro-IQ induced significant SCEs to a plateau level of 0.90 per chromosome. Cytogenetic damage in the liver by IQ was greater than that by nitro-IQ. These results show that this assay of chromosome aberrations and SCEs in rat liver in vivo without partial hepatectomy or mitogen treatment in vivo is a sensitive method for evaluating the cumulative tumor-initiating activities of carcinogenic heterocyclic amines at low doses and should be useful for the detection of unknown hepatocarcinogens.

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