Differential effects of chronic alcohol administration to rats on the activation of aromatic amines to mutagens in the Ames test

Abstract

Male Wistar albino rats were maintained on alcohol-containing liquid diets for 4 weeks. Hepatic post-mitochondrial preparations derived from these animals were more efficient than control in activating 4-aminobiphenyl and 2-aminofluorene to mutagens in the Ames test. The alcohol-induced enhancement in mutagenicity was not inhibited by dimethylsulphoxide indicating that the generation of hydroxyl radicals is not involved. The activation of 2-naphthylamine was not affected by the treatment with alcohol but the mutagenicities of 2-aminoanthracene, benzo[a]pyrene and 3-methylcholanthrene were inhibited. The same treatment markedly increased hepatic microsomal aniline p-hydroxylase and ethoxyresorufin O-de-ethylase activities and to a lesser extent benzphetamine N-demethylase and microsomal levels of total cytochromes P-450. It is concluded that chronic alcohol administration to rats modulates the metabolic activation of pre-carcinogens to their reactive intermediates presumably by causing the redistribution of cytochrome P-450 isozymes.

Liver Microsomal Mixed-Function Oxidases in Response to Dietary Whole Egg Protein Levels in Rats.

“…Cytochromes P-448, a distinct family of cytochromes induced typically by 3 methylcholanthrene, direct the metabolism of chemical carcinogens towards the formation of reactive intermediates (36), and similarly, the cytochromes P-450 induced by ethanol, preferentially catalyze the activation of nitrosamines and some aromatic amines (37,38). In contrast, cytochromes P-450 induced by PB exhibit primarily a deactivating role, leading also to the ultimate detoxication of chemical carcinogens (36).…”