The mechanism of cocarcinogenic action of ethanol in rat liver.
The effects of chronic alcohol consumption on nitrosamine metabolism in vivo, DNA synthesis and repair, and carcinogen-induced preneoplasia were studied in rat liver. Following a single injection of different doses of 14C-N-nitrosodimethylamine, there was no significant difference between controls and ethanol-pretreated rats in the alkylation pattern of cellular protein nor in the levels of the alkylation products 7-methylguanine and O6-methylguanine isolated from liver DNA. O6-Methylguanine-specific DNA repair was also unchanged. An increase in the number and size of foci staining negative for adenosine triphosphatase and/or positive for gamma-glutamyltranspeptidase was observed in rats treated intermittently with ethanol and N-nitrosomorpholine. The numbers of clear-cell and mixed-cell foci were also increased. An ethanol-mediated enhancement of DNA synthesis, which was ascertained by different methods, may be related to this cocarcinogenic action of the alcohol. Ethanol, however, failed to demonstrate promoting activity. Long-term treatment of carcinogen pretreated rats with ethanol, according to the classical initiation-promotion protocol, had no effect on the incidence of preneoplastic foci in liver.
D000818:Animals; D002273:Carcinogens; D004261:DNA Replication / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats
D002273:Carcinogens; D009602:Nitrosamines; D000431:Ethanol; C002741:N-nitrosomorpholine; D004128:Dimethylnitrosamine