Carcinogenesis in syrian hamsters by N-nitroso-2, 6-dimethyl-morpholine, its cis and trans isomers, and the effect of deuterium labeling

Groups of 20 Syrian male golden hamsters were treated by gavage with solutions of the cis and trans isomers of N-nitroso-2, 6-dimethylmorpholine in olive oil. Two doses of each isomer were given for the same time and the ratios of the concentrations corresponded with the ratio in the normally prepared mixture, 2 parts cis to 1 part trans. The cis isomer was more potent in inducing tumors of the liver and pancreas than the trans isomer. The effect of replacement of hydrogen with deuterium at the positions alpha and beta to the nitroso function on carcinogenic poténcy was examined by administering by gavage the respective isotopically labeled compounds to groups of 20 male hamsters. Each labeled sample constituted a mixture of cis and trans isomers in the ratio of approximately 2 to 1, and the dose was identical with that of the unlabeled sample of the nitrosamine. The beta deuterium labeled compound was less carcinogenic and the alpha deuterium labeled compound was more carcinogenic than the unlabeled material. There was no significant difference between the isomers in activation to a bacterial mutagen by pancreas microsomes or in binding to DNA of the pancreas.