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

Male Wistar rats were treated for 2 weeks with 20% ethanol inthe drinking water. Twenty four hours after the terminationof treatment animals were injected with different doses of [¹⁴C]dimethylnitrosamineand killed 4 h thereafter. The amounts of 7-methylguanine andO⁶-methylguanine present in liver DNA were determined. Therewas no significant difference in the levels of either DNA alkylationproduct between untreated controls and animals pre-treated withethanol. The O⁶-methylguanine/7-methylguanine ratio was alsounchanged. Specific radioactivity levels in the cellular proteinof [¹⁴C]dimethylnitrosamine injected animals were slightly loweredafter ethanol pre-treatment. In contrast, incorporation of labelledguanine into liver DNA was greatly enhanced at all DMN dosesin ethanol pre-treated animals indicating an increase in DNAsynthesis. This enhancement of DNA synthesis was confirmed atdifferent ethanol doses, given either in the drinking wateror by stomach tube, by the increase in specific radioactivityof liver DNA and the increase in the number of labelled nucleifollowing [³H]thymidine pulse-labelling.