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Inhibition of Methylazoxymethanol-induced Intestinal Tumors in the Rat by Pyrazole with Paradoxical Effects on Skin and Kidney¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

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.

¹ Supported by USPHS Grants CA 08748 from the National Cancer Institute and CA 15637 from the National Cancer Institute through the National Large Bowel Cancer Project.

² Visiting scientist at the Laboratory of Pharmacology, Memorial Sloan-Kettering Cancer Center. Permanent address: Abteilung für Toxikologie und Experimentelle Pathologie, C. H. Boehringer Sohn, 6507 Ingelheim am Rhein, Federal Republic of Germany.

³ To whom requests for reprints should be addressed.

Received 9/ 2/81. Accepted 1/26/82.

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