Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats

Abstract

The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.