Effect of ethanol on early stages in nitrosamine carcinogenesis in rat liver.

The effect of chronic alcohol consumption on the extent of adenosine triphosphatase(ATPase)-deficient preneoplastic lesions in rat liver induced by either diethylnitrosamine (DEN) (3 mg/kg, p.o.) or N-nitrosomorpholine (NNM) (40 ppm in the drinking water) was studied. Carcinogens were administered on 4 days in every week for 11 (DEN) and 15 (NNM) weeks, respectively. Ethanol was given at a concentration of 10% (w/v) in the drinking water either during carcinogen treatment or after withdrawal of carcinogen. An increase in both number and size of ATPase-deficient foci in liver was observed when the alcohol was given during the period of carcinogen administration. This increase may be associated with the known toxic action of ethanol which leads to single cell necrosis and liver regeneration. In contrast, when ethanol (10% in the drinking water for 16 weeks) was given after cessation of carcinogen treatment following a tumor-promotion feeding protocol, no such enhancement in preneoplastic response was obtained. Ethanol alone was ineffective in inducing ATPase-deficient foci. In liver, ethanol thus appears to possess, under certain conditions, co-carcinogenic but not tumor-promoting capacity.