N-NITROSO-N-METHYLVINYLAMINE - REACTION OF THE EPOXIDE WITH GUANYL AND ADENYL MOIETIES TO YIELD ADDUCTS DERIVED FROM BOTH PARTS OF THE MOLECULE

N-Nitroso-N-methylvinylamine was synthesized and treated with dimethyldioxirane to produce 1-(N-nitrosomethylamino)oxirane. 1-(N-Nitrosomethylamino)oxirane had a t1/2 of <5 s in buffer at neutral pH and 23-degrees-C. This epoxide reacted with Ado to form 1,N6-etheno(epsilon-)Ado. It also reacted with DNA to form products arising from the oxirane portion of the molecule [N7-(2-oxoethyl) Gua, N2,3-epsilon-Gua, and 1,N6-epsilon-dAdo] and the methyl group (N7-methylGua). NADPH-fortified rat liver microsomes oxidized N-nitroso-N-methylvinylamine to form 1,N6-epsilon-Ado in the presence of Ado. Further, 1,N6-epsilon-Ado was also formed in microsomal incubations containing N-nitroso-N-methylethylamine, indicating that desaturation of the ethyl moiety occurs to form a vinyl group and then an epoxide. When NADPH-fortified microsomes were incubated with N-nitroso-N-methylvinylamine, HCHO was formed, and when DNA was included in incubations, 1,N6-epsilon-dAdo and N7-methylGua were isolated from DNA. In the cases of both HCHO and N7-methylGua, product formation was similar to the levels seen with N-nitroso-N,N-dimethylamine and N-nitroso-N-methylethylamine.