title: N-nitroso-N-methylvinylamine: reaction of the epoxide with guanyl and adenyl moieties to yield adducts derived from both parts of the molecule.
abstract: 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.
authors: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
authors: O
authors: O
authors: Okazaki
authors: M
authors: M
authors: Persmark
authors: F P
authors: FP
authors: Guengerich
mesh_terms: D000225:Adenine / Q000737:chemistry; D000818:Animals; D002273:Carcinogens / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D014753:Vinyl Compounds / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; D009603:Nitroso Compounds; D014753:Vinyl Compounds; C080849:1-(N-nitrosomethylamino)oxirane; C080848:N-nitroso-N-methylvinylamine; D006147:Guanine; D004247:DNA; D000225:Adenine