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Chronic ethanol consumption inhibits repair of dimethylnitrosamine-induced DNA alkylation
S I Mufti1, M Salvagnini, C S Lieber
1Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
Abstract:
Chronic ethanol consumption causes a DNA repair deficiency. This was demonstrated in Sprague-Dawley rats injected with 14C-labeled dimethylnitrosamine after being pair-fed isocaloric, ethanol, or carbohydrate control diets for 4 weeks. Hepatic DNA was isolated from rats killed at intervals over a 36 hour period after administration of the nitrosamine and concentrations of alkylated guanine derivatives were measured. While N7-methylguanine was lost at equivalent rates from the DNA of both diet groups, 06methylguanine, a promutagenic lesion, persisted at higher levels for longer periods of time in the DNA from the alcohol-fed animals.