Comparative carcinogenicity of N-nitrosobis(2-oxopropyl)amine and N-nitrosomethyl(2-oxopropyl)amine following subcutaneus or oral administration to rats

Abstract The carcinogenicity of N-nitrosomethyl(2-oxopropyl)amine (MOP), a postulated proximate carcinogen of N-nitrosobis(2-oxopropyl)amine (BOP), was tested after either a single subcutaneous (s.c.) injection or weekly intragastric (i.g.) administration in Wistar-derived MRC rats and was compared with the effect of BOP, given similarly and at equitoxic doses. Following i.g. administration, MOP induced a high incidence of neoplasms in the pharynx and esophagus which, however, were not affected by BOP; on the other hand, tumors of the thyroid, lungs, colon and urethra occurred in a greater incidence following BOP than after MOP, and renal neoplasms were found only following MOP, given s.c. Moreover, there were remarkable sex differences in the responses of the rats' respiratory and urothelial tissues to these two carcinogens: nasal cavity carcinomas, pulmonary adenomas, urinary and urethra papillomas were induced primarily or exclusively in male rats treated with BOP, either s.c. or i.g., whereas such sex differences were not found following either route of MOP administration. There were also differences in the spectrum of the neoplasms induced by BOP or MOP depending upon the route of their administration. For example, MOP was more effective in inducing nasal, esophageal and hepatic tumors when given orally, compared to its effect following the s.c. route, and thyroid and renal tumors were induced only after its s.c. injection. The results point to a complexity of nitrosamine carcinogenesis and also indicate that in some tissues activation of BOP, but not of MOP, depends on sex hormones.