Effect of ethanol on dimethylnitrosamine activation and DNA synthesis in rat liver

Male Wistar rats were treated for 2 weeks with 20% ethanol in the drinking water. Twenty four hours after the termination of treatment animals were injected with different doses of [14C]dimethylnitrosamine and killed 4 h thereafter. The amounts of 7-methylguanine and O6-methylguanine present in liver DNA were determined. There was no significant difference in the levels of either DNA alkylation product between untreated controls and animals pre-treated with ethanol. The O6-methylguanine/7-methylguanine ratio was also unchanged. Specific radioactivity levels in the cellular protein of [14C]dimethylnitrosamine injected animals were slightly lowered after ethanol pre-treatment. In contrast, incorporation of labelled guanine into liver DNA was greatly enhanced at all DMN doses in ethanol pre-treated animals indicating an increase in DNA synthesis. This enhancement of DNA synthesis was confirmed at different ethanol doses, given either in the drinking water or by stomach tube, by the increase in specific radioactivity of liver DNA and the increase in the number of labelled nuclei following [3H]thymidine pulse-labelling.