Chronic alcoholism enhances hepatocarcinogenicity of diethylnitrosamine in rats fed a marginally methyl-deficient diet
✍ Scribed by Eduardo A. Porta; Nalani Markell; Russell D. Dorado
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 724 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
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 g r o u p were offered a drinking ethanol solution, while two other nonalcohol control g r o u p (C and D) were isocalorically pair-fed to Groups A and B, and received diets in which the alcohol consumed by the corresponding g r o u p was replaced by h a l o r i c amounts of sucrose. A baseline nonalcohol Group E, ieocalorically pairfed 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 statisticlly 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.
All prospective and retrospective case-control studies indicate that the incidence of primary hepatocellular carcinoma (PHC) among alcoholics is above expected normal levels (1, for review). Although a proportion of alcohol drinkers with PHC may also have hepatitis B virus antigens (2,3), and/or cigarette smoking habits (4, 5), these risk factors for PHC may be found independently (4).
The pathogenesis of PHC in human alcoholics has not yet been d b l h h e d (6), and all attempts to reproduce thie condition in erperimental animals have invariably failed. When animals not treated with any hepatmarcinogen were chronically fed commercial rations and were offered ethanol eolutions of various strength^, they never developed PHC or even preneoplaetic hepatic foci (7-10). Chronic alcoholics consume, of course, not pure