Comparison of carcinogenesis by two isomers of nitroso-2,6-dimethylmorpholine

The cis and trans isomers of nitroso-2,6-dimethylmorpholine (Me2NMOR) have been separated and administered to Fischer 344 rats at doses corresponding to their proportion in the mixture prepared from the commercial amine (approximately 2 cis to 1 trans). The mixture of isomers was given at 2 doses, 50 mg per liter of drinking water and 20 mg per liter. A standard volume of each solution was given (20 ml per day per rat) on 5 days of each week and the animals were treated for the same time at either higher or lower dose levels. Almost all of the animals died with basal cell carcinomas and/or papillomas of the upper gastrointestinal tract. The time at which the rats died with the tumors was used as a measure of carcinogenic potency. Survival of the treated animals was consistently longer at the lower dose of each isomer. It was concluded that the trans isomer of Me2NMOR is a more potent carcinogen in rats than the cis isomer.