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

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Abstract
Male Wistar rats were treated for 2 wk with 20% ethanol in the drinking water. After the termination of treatment (24 h) animals were injected with different doses of [14C]dimethylnitrosamine [DMN] 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]DMN injected animals were slightly lowered after ethanol pre-treatment. Incorporation of labeled 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 labeled nuclei following [3H]thymidine pulse-labeling. [This study may be applicable to carcinogenesis.].