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[Cancer Research 38, 3793-3804, November 1, 1978]
© 1978 American Association for Cancer Research

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Vinyl Carbamate as a Promutagen and a More Carcinogenic Analog of Ethyl Carbamate1

Gary A. Dahl, James A. Miller2 and Elizabeth C. Miller

McArdle Laboratory for Cancer Research, University of Wisconsin Center for Health Sciences, Madison, Wisconsin 53706

Vinyl carbamate was much more active (10 to 50 times) than ethyl carbamate for the initiation of skin tumors and for the induction of lung adenomas in mice. Vinyl carbamate was also mutagenic to Salmonella typhimurium TA 1535 and TA 100 in the presence of reduced nicotinamide adenine dinucleotide phosphate-fortified rat or mouse liver mitochondrial supernatant fractions. This mutagenic activity was inhibited strongly by cytochrome P-450 inhibitors. No mutagenic activity was observed for vinyl carbamate in the absence of added liver preparations or for ethyl carbamate in the presence or absence of liver fractions.

Extensive tests with sensitive methods failed to detect vinyl carbamate as a metabolite of ethyl carbamate in the mouse in vivo. However, on administration of [ethyl-1-14C;1,2-3H]ethyl carbamate to adult mice the 3H/14C ratios of the hepatic DNA-, rRNA-, and protein-adducts were similar to each other and much lower than the ratio of the administered ethyl carbamate. These data are consistent with the presence of desaturated and/or oxidized ethyl groups in the macromolecular adducts. The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis.

1 In honor of the 70th birthday of Dr. Harold P. Rusch, M. D., founder and long-time Director of the McArdle Laboratory for Cancer Research and creator of its productive research atmosphere.

This work was supported by Grants CA-07175, CA-15785, CA-22484, and CA-09135 from the National Cancer Institute, USPHS.

2 To whom requests for reprints should be addressed.

Received 6/26/78. Accepted 8/14/78.




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Copyright © 1978 by the American Association for Cancer Research.