Augmentation of ethanol-induced enhancement of dimethylnitrosamine and diethylnitrosamine metabolism by lowered carbohydrate intake.

Hepatic metabolism in vitro of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), 3,4-benzopyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) was assayed using the liver of rats maintained for 3 weeks on liquid diets containing three levels of carbohydrate (CHO) with or without supplementation of ethanol (5 g/100 ml). Ethanol consumption increased the metabolism of DMN and DEN to different degrees depending on the diet consumed simultaneously. Lowered CHO intake, which by itself increased the metabolism, dose-dependently augmented the increase due to ethanol: the lower the CHO intake, the more remarkable was the enhancement caused by ethanol. Ethanol increased microsomal cytochrome P-450 content only when combined with low-CHO diets. It was confirmed by a Salmonella mutagenicity test that the enhancement of DMN and DEN metabolism was accompanied by increased capacity of the liver to activate these nitrosamines to mutagens. On the other hand, neither lowered CHO intake, nor ethanol consumption, nor their combination affected the metabolism of BP and DMBA. Ethanol combined with a diet deficient in CHO even suppressed the metabolism of BP.