CARCINOGENICITY OF N-NITROSOMETHYL(2-OXOPROPYL)AMINE IN SYRIAN-HAMSTERS

Abstract

The carcinogenicity of a potential methylating metabolite of BOP [N-nitrosobis(2-oxopropyl)amine], N-nitrosomethyl(2-oxopropyl)amine (MOP), was examined. MOP was a potent pancreatic carcinogen in Syrian golden hamsters by single or weekly s.c. injections. A single MOP treatment (25 mg/kg body wt) induced ductular adenomas and/or adenocarcinomas in 80% of the hamsters. A higher incidence of these neoplasms was found in 93% and 87% of animals receiving, respectively, 3.5 and 1.75 mg MOP per kg body weight weekly for life. The lower dose (0.87 mg/kg body wt) was less effective, resulting in a 33% tumor incidence. Compared with the known potent pancreatic carcinogen BOP, MOP seemed to have a greater affinity for the pancreas since considerably lower doses were required to induce similar incidences of equivalent pancreatic tumors. Like BOP, MOP caused tumors of the liver (7-100% incidence), kidneys (7-80% incidence) and vascular system (7-27% incidence). In contrast to BOP, which was noncarcinogenic to the upper respiratory tract, MOP-treated animals developed a high incidence of nasal cavity tumors (40% after a single treatment and 27-100% after weekly injections). The mutagenesis studies using hamster liver cell-mediated V79 cells confirmed the stronger effect of MOP compared to BOP. The assumption that MOP might be a proximate carcinogenic metabolite of BOP could not be substantiated.