Carcinogenicity of N-nitrosomethyl(2-oxopropyl)amine in Syrian hamsters.
7-Methylguanine was found in hydrolysates of liver and pancreas DNA from Syrian golden hamsters given a single dose of N-[1-14C]nitrosobis(2-oxopropyl)amine (BOP). This led us to examine the carcinogenicity of a potential methylating metabolite of BOP, N-nitrosomethyl(2-oxopropyl)amine (MOP). MOP was found to be a potent pancreatic carcinogen by either single or weekly s.c. injections. A single MOP treatment (25 mg/kg body weight) 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. However, the lower dose (0.87 mg/kg body weight) 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 to 100% incidence), kidneys (7 to 80% incidence), and vascular system (7 to 27% incidence). However, 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 to 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 by our methods for determining the in vivo and in vitro metabolites of BOP.
D000230:Adenocarcinoma / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D002273:Carcinogens; D002460:Cell Line; D006224:Cricetinae; D004067:Digestive System Neoplasms / Q000139:chemically induced; D005260:Female; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D008647:Mesocricetus; D009153:Mutagens; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009378:Neoplasms, Multiple Primary / Q000139:chemically induced; D009602:Nitrosamines / Q000097:blood / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009153:Mutagens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine