Effect of Ethanol Consumed in Combination with High or Low Fat Diets on the Postinitiation Phase of Hepatocarcinogenesis in the Rat

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Abstract
In this study, the effect of chronic ethanol ingestion on the modification of the postinitiation phase of hepatocarcinogenesis was examined. Hepatic lesions were initiated in Sprague-Dawley rats by administration of 10 doses of aflatoxin B1 (AFB1) over a 2-week period. Following a week of acclimation rats were fed ethanol (35% of caloric intake) in low fat (11% of calories) or high fat (35% of calories) AIN-76-based liquid diets according to a unique feeding regime for 12 weeks. The effect of ethanol on the development of hepatic γ-glutamyltransferase (GGT)-positive foci and on nutrient status was evaluated. Only those rats consuming ethanol with a high fat diet developed fatty livers, but all those consuming ethanol had low hepatic vitamin A and glutathione levels compared to pair-fed and ad libitum-fed controls. Despite these changes, no effect of ethanol consumption on the formation of GGT-positive foci was observed. Rats fed a high fat diet had an increased number and size of foci compared to rats on a low fat diet (P ≤ 0.01). It was concluded that despite these effects of ethanol on several physiological parameters, modification of the development of presumptive preneoplastic hepatic foci was not affected.