Comparative carcinogenesis by nitrosomorpholines, nitrosooxazolidines and nitrosotetrahydrooxazine in rats

A comparison was made of the carcinogenic effectiveness of some cyclic nitrosamines containing oxygen in the ring. The compounds were administered to F344 rats at approximately equimolar concentrations in drinking water. Nitrosomorpholine, nitroso-1,3-oxazolidine and nitrosotetrahydro-1,3-oxazine were of similar potency and gave rise to hepatocellular carcinomas and angiosarcomas of the liver in almost 100% of treated rats. Methyl substitution at the beta position of nitrosomorpholine increased the potency, but retained the main target organ as the liver, while methyl substitution at both beta positions resulted in a further increase in potency, but elimination of the liver as a target and with the main site of tumor induction the upper gastrointestinal tract. In contrast, methyl substitution in the beta position of nitrosooxazolidine resulted in a decrease in carcinogenic potency, but with 100% incidence of liver tumors, but relatively few angiosarcomas. A methyl group at the 2-position of nitrosooxazolidine also reduced carcinogenic potency, all of the animals dying with liver tumors, but few angiosarcomas, but the change was no larger than that produced by the presence of methyl at the 5-position (beta).