Differential effects of chronic alcohol administration to rats on the activation of aromatic amines to mutagens in the Ames test.
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.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003580:Cytochromes / Q000096:biosynthesis; D000431:Ethanol / Q000633:toxicity*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D006900:Hydroxylation; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D010105:Oxygenases / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D002273:Carcinogens; D003580:Cytochromes; D006878:Hydroxides; D009153:Mutagens; D017665:Hydroxyl Radical; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2