Metabolism and Mutagenicity of N-Nitroso-2-methoxy-2,6-dimethylmorpholine in Hamsters

Abstract

N-Nitroso-2- methoxy-2,6-dimethylmorpholine (MeNDMM) was derived from the cyclic form of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), a proposed proximate pancreatic carcinogen for the hamster. MeNDMM was metabolized in vivo by nonlnbred Syrian golden hamsters to HPOP, which was excreted in urine. In vitro metabolism produced HPOP by cytochrome P₄₅₀-mediated oxidative demethylation. MeNDMM and HPOP were similarly mutagenic in the Ames Salmonella typhimurium assay, in which hamster liver preparations were used for metabolic activation. MeNDMM, due to its metabolism to HPOP, is probably also a pancreatic carcinogen in the hamster.