Carcinogenesis by nitrosodialkylamines and azoxyalkanes given by gavage to rats and hamsters

The carcinogenic effects of three nitrosamines, nitrosodimethylamine (NDMA), nitrosodiethylamine (NDEA), and nitrosomethylethylamine (NMEA), and two azoxyalkanes, azoxymethane and azoxyethane, have been compared by administration by gavage of multiple equimolar doses to F344 rats and Syrian golden hamsters. NDMA and azoxymethane were severely toxic to hamsters, requiring the use of lower dose rates. In hamsters, the most commonly observed tumors were hepatocellular, cholangiocellular, and vascular tumors of the liver, but azoxyethane, NMEA, NDMA, and NDEA also induced tumors of the nasal mucosa, and azoxymethane induced tumors of the colon. In hamsters, NDEA and azoxyethane were less potent carcinogens than the corresponding methyl compounds, NDMA and azoxymethane. In contrast, in rats the two ethyl compounds were more potent than the corresponding methyl compounds, and NMEA was intermediate in potency. In rats, all three nitrosamines commonly induced liver tumors, mostly hepatocellular, but few liver tumors were induced by the two azoxyalkanes. Instead, azoxymethane induced colon tumors and azoxyethane induced tumors of the nasal mucosa. When given by gavage, NDMA induced a high incidence of mesenchymal tumors of the kidney and alveolar-bronchiolar tumors of the lungs as well as liver tumors.