Chronic alcoholism enhances hepatocarcinogenicity of diethylnitrosamine in rats fed a marginally methyl-deficient diet.
To determine whether the chronic consumption of ethanol was capable of enhancing the hepatocarcinogenic activity of diethylnitrosamine per se, or through the accentuation of a methyl deficiency, two groups (A and B) of Sprague-Dawley female rats were fed for 10 months either a 20% casein basal diet marginally deficient in methyl, or the same diet supplemented with choline (1 gm per 100 gm) and folic acid (0.54 mg per 100 gm). Both groups were offered a drinking ethanol solution, while two other nonalcohol control groups (C and D) were isocalorically pair-fed to Groups A and B, and received diets in which the alcohol consumed by the corresponding groups was replaced by isocaloric amounts of sucrose. A baseline nonalcohol Group E, isocalorically pair-fed to Group A, received the intact basal diet of Group A and water. One day before the initiation of the experiment, and again 2 months later, all rats from the five groups were injected with a single i.p. dose of diethylnitrosamine (100 mg per kg). The growth attained by all groups was statistically similar. Hepatic triglycerides in Group A were significantly higher than in all the other groups. While in Group A primary hepatocellular carcinomas and renal tumors were encountered at the end of the experiment in 3 of 6 and in 2 of 6 rats, respectively, no malignancies were observed in any of the other groups. These results indicate that chronic ethanol consumption enhances the hepatocarcinogenic and renal tumorigenic activity of diethylnitrosamine, and strongly suggest that this action is mediated through the accentuation of methyl deficiency.
D000437:Alcoholism / Q000150:complications*; D000818:Animals; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000633:toxicity*; D002149:Energy Intake; D000431:Ethanol / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D004052:Diethylnitrosamine; D000431:Ethanol