Increased carcinogenicity of 2,6-dimethylnitrosomopholine compared with nitrosomopholine in rats

Nitrosomorpholine was given to rats in drinking water at the rate of 4 mg/week for 30 weeks. Tumors of the liver were induced in 53% of treated animals and were of both hepatocellular and Kupffer cell origin. One-half of the treated animals were alive 75 weeks after the beginning of treatment, but only 2 survived to 104 weeks. 2,6-Dimethylnitrosomopholine was given to rats at the same molar concentration in drinking water for 30 weeks (5 mg/week). All of these animals died with tumors within 34 weeks after the beginning of treatment; these tumors were mainly in the esophagus and nasal turbinates, and only 1 liver tumor was seen. This greatly changed tumorigenicity of the dimethyl compound might be due to steric factors or to enhanced reactivity at the positions alpha to the nitroso function induced by the methyl groups at the beta position.