Histochemical findings suggesting that methylazoxymethanol, a liver and kidney carcinogen, is a substrate for hepatic and renal choline dehydrogenase.
Methylazoxymethanol (MAM) is a potent carcinogen and induces tumors predominantly in rat liver, colon and kidney. The findings reported in this paper suggest that MAM is a substrate for the enzyme choline dehydrogenase located in rat hepatocytes and in the terminal portion of the renal proximal convoluted tubule. As with the natural substrate choline, this reaction with MAM did not require NAD+, was not inhibited by pyrazole and was dependent on the electron transfer reagent, phenazine methosulfate. The product of this reaction is probably the same as that obtained from the metabolism of MAM by alcohol dehydrogenase, namely, an unstable aldehydic derivative which decomposes rapidly to carbonium ions. The reaction with alcohol dehydrogenase offered an explanation for the organotropic effects of this carcinogen in liver and colon and the current report provides a mechanism for the induction of kidney tumors as well as another possible means for production of liver tumors.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D050545:Choline Dehydrogenase; D006651:Histocytochemistry; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; D000429:Alcohol Oxidoreductases; D050545:Choline Dehydrogenase