Inhibition of methylazoxymethanol-induced intestinal tumors in the rat by pyrazole with paradoxical effects on skin and kidney.
Methylazoxymethanol is a potent carcinogen and induces tumors predominantly of the small intestine and colon following a single injection. Previous data indicated that alcohol dehydrogenase could convert this carcinogen to a reactive alkylating agent. Rats were treated with an inhibitor of this enzyme, pyrazole, 2 hr prior to their receiving the carcinogen. The development of intestinal and colonic tumors was prevented. The rats did, however, develop numerous tumors of the skin and kidney. Analyses of the complete autopsies are presented. The data indicate that intestinal and colonic alcohol dehydrogenase plays a role in the tumorigenic effects of methylazoxymethanol and that other non-pyrazole-sensitive enzymes exist in other organs that can also activate this carcinogen.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001391:Azo Compounds; D001711:Biotransformation; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008746:Methylazoxymethanol Acetate; D011720:Pyrazoles / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology
D001391:Azo Compounds; D011720:Pyrazoles; D008746:Methylazoxymethanol Acetate; D000429:Alcohol Oxidoreductases