ORGAN-SPECIFIC CARCINOGENESIS IN RATS BY METHYLAZOXYALKANES AND ETHYLAZOXYALKANES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 76-79
Abstract
Azoxyalkanes are isomeric with nitrosodialkylamines and could be similar in their biochemical and biological actions. To compare the structure-activity relations in the 2 series, the tumorigenic activites of 4 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 wk, but at the higher dose of the 2 ethylazoxy compounds, 24 wk of treatment were sufficient. Most of the animals died with tumors that could be attributed to the treatments. The 2 ethylazoxy compounds caused much earlier death from tumors than the corresponding methylazoxy compounds. All 4 compounds induced a high incidence of liver neoplasms, which were mainly hepatocellular; the 2 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. The biochemical activation of azoxyalkanes evidently is different from the analogous nitrosodialkylamines.