Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats.
The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.
Department of Environmental Health, Medical University of Yamanashi, Japan.
I
I
Yonekura
Y
Y
Matsumoto
K
K
Miura
A
A
Sato
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003043:Cocarcinogenesis; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004052:Diethylnitrosamine; D000431:Ethanol / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D004040:Dietary Carbohydrates; D004052:Diethylnitrosamine; D000431:Ethanol; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase