The effect of deuterium labeling on the carcinogenicity of nitroso-2,6-dimethylmorpholine in rats

Nitroso-2,6-dimethylmorpholine (Me2NMOR) was labeled with deuterium in either the alpha or beta positions. Both the deuterium-labeled, and the unlabeled, compounds were administered to female Fischer 344 rats at equimolar concentrations in drinking water. The animals were then allowed to die naturally with tumors. The parent compound and the alpha-d4-labeled derivative were given at 50 mg/liter and 20 mg/liter, while, because of a shortage of the compound, the beta-d2-labeled derivative was given only at 20 mg/liter. Almost all of the animals died with basal cell carcinomas and papillomas of the esophagus; many animals fed the lower doses also had tumors of the nasal cavity and tongue. The rate of death from induced tumors was lower in the alpha-d4-treated group than in those treated with the unlabeled compound (at both dose levels), but was higher in the rats treated with the beta-d2 compound. It appears that deuterium in the alpha positions decreases carcinogenic potency, while deuterium in the beta positions increases it. This suggests that oxidation at the beta carbon atoms is less likely to be involved in esophageal carcinogenesis in the rat by Me2NMOR than is oxidation at the alpha carbon atoms.