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Inhibition of 1,2-Dimethylhydrazine Metabolism by Disulfiram

Emerich S. Fiala, George Bobotas, Callie Kulakis, John H. Weisburger

Abstract

1. The effects of disulfiram on the metabolism of 1,2-dimethylhydrazine were studied in CDF rats. 2. Treatment with disulfiram causes enhanced elimination of azomethane in the expired air, inhibition of CO2 production, and decreased levels of 1,2-dimethylhydrazine metabolites in the urine. 3. These results suggest that disulfiram inhibits the N-oxidation of azomethane to azoxymethane, thus preventing further metabolism to the ultimate carcinogenic species, and provide an explanation for the observations that disulfiram inhibits 1,2-dimethylhydrazine-induced neoplasia of the large intestine.

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Key concepts: Disulfiram, Dimethylhydrazine, 1,2-Dimethylhydrazine, Chemistry, Metabolism, Carcinogen, Pharmacology, Azoxymethane