Differential Metabolism of Geometrical Isomers of N-Nitroso-2, 6-dimethylmorpholine in the Hamster

Abstract

1. The cis and trans isomers of the pancreatic carcinogen N-nitroso-2,6-dimethylmorpholine have been prepared separately, and their metabolism studied in the Syrian hamster.

2. Both isomers were metabolized by β-oxidation and ring scission to N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, the suggested proximate pancreatic carcinogen, and to N-nitrosobis(2-hydroxypropyl)amine.

3. The initial rate of β-oxidation and urinary excretion of the cis isomer was much greater than for the trans isomer, and this is explained in terms of relative ease of enzymic axial attack. The amounts of metabolites in the 24-h urine were, however, similar.

4. The results suggest that the two isomers would have no different carcinogenic potency with respect to the hamster pancreas.