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Organ-specific Carcinogenesis in Rats by Methyl- and Ethylazoxyalkanes¹

LBI-Basic Research Program, Chemical Carcinogenesis Program, National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland 21701

Azoxyalkanes are isomeric with nitrosodialkylamines and could be similar in their biochemical and biological actions. To compare the structure-activity relations in the two series, the tumorigenic activities of four azoxyalkanes, azoxymethane, azoxyethane, Z-ethyl-O,N,N-azoxymethane, and Z-methyl-O,N,N-azoxyethane, were compared in male F344 rats by p.o. administration of 0.54 mM and 0.135 mM solutions in drinking water. In most cases, treatment lasted 30 weeks, but at the higher dose of the two ethylazoxy compounds, 24 weeks of treatment were sufficient. Most of the animals died with tumors that could be attributed to the treatments. The two ethylazoxy compounds caused much earlier death from tumors than the corresponding methylazoxy compounds. All four compounds induced a high incidence of liver neoplasms, which were mainly hepatocellular; the two ethylazoxy compounds also induced a large number of hemangiosarcomas in the liver. At both dose levels, azoxyethane induced tumors of the esophagus and nasal cavity, tumors that were not seen in any other group. Other tumors appearing in significant incidence were in the colon and ileum, induced by azoxymethane and Z-ethyl-O,N,N-azoxymethane, and kidney tumors induced by azoxymethane and Z-methyl-O,N,N-azoxyethane. In F344 rats, azoxyethane was similar in carcinogenic activity to its isomer nitrosodiethylamine, whereas azoxymethane was much less potent than nitrosodimethylamine and induced quite different tumors. These results suggest that the biochemical activation of azoxyalkanes is different from the analogous nitrosodialkylamines.

¹ Research sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23909 with Litton Bionetics, Inc.

² To whom requests for reprints should be addressed.

³ Present address: 11014 Swansfield Rd., Columbia, MD 21044.

Received 4/30/84. Accepted 9/19/84.

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