CUMULATIVE EFFECTS OF CHROMOSOME-ABERRATIONS AND SISTER-CHROMATID EXCHANGES IN RAT-LIVER INDUCED IN-VIVO BY HETEROCYCLIC AMINES

Cumulative effects of chromosome aberrations and sister chromatid exch anges (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 o r 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f]quinoline (nit ro-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 gast ric intubation and allowed to proliferate in Williams' medium E supple mented with epidermal growth factor. Cells were fixed after a culture period of 48 h. Multiple treatment with IQ or nitro-IQ induced signifi cant chromosome aberrations time- and dose-dependently, the maximum fr equency of chromosome aberrations in metaphase cells being 39 and 33% respectively, while that in controls was 1.1%. Single treatment with I Q or nitro-IQ induced significant SCEs dose-dependently, the maximum f requency being 0.83 and 0.79 per chromosome respectively, while the co ntrol value was 0.51. Multiple treatment with nitro-IQ induced signifi cant SCEs to a plateau level of 0.90 per chromosome. Cytogenetic damag e 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 i n vivo without partial hepatectomy or mitogen treatment in vivo is a s ensitive method for evaluating the cumulative tumor-initiating activit ies of carcinogenic heterocyclic amines at low doses and should be use ful for the detection of unknown hepatocarcinogens.