Effect of ethanol consumed in combination with high or low fat diets on the postinitiation phase of hepatocarcinogenesis in the rat.
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 gamma-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 less than or equal to 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.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000009:adverse effects*; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D008107:Liver Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014801:Vitamin A / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000348:Aflatoxins; D004041:Dietary Fats; D014801:Vitamin A; D000431:Ethanol; D016604:Aflatoxin B1; D005723:gamma-Glutamyltransferase