title: Comparative mutagenicity of 4-(carbethoxynitrosamino)-4-(3-pyridyl)butanal and 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone, model compounds for alpha-hydroxylation of N'-nitrosonornicotine.
abstract: 4-(Carbethoxynitrosamino)-1-(3-pyridyl)butanal, a stable precursor to the putative diazohydroxide formed by 5'-hydroxylation of the tobacco-specific nitrosamine, N'-nitrosonornicotine, was synthesized in six steps from nicotinaldehyde. Its mutagenicity toward S. typhimurium was compared to that of 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone, a precursor to the diazohydroxide formed by 2'-hydroxylation of N'-nitrosonornicotine. At equimolar doses, 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone was a potent mutagen, but 4-(carbethoxynitrosamino)-1-(3-pyridyl)butanal was inactive toward strains TA 100 and TA 1535. The results of this study indicate that the putative diazohydroxide formed by 2'-hydroxylation of N'-nitrosonornicotine has higher inherent mutagenicity toward S. typhimurium than does the corresponding diazohydroxide formed by 5'-hydroxylation.
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009602:Nitrosamines / Q000378:metabolism* / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D009602:Nitrosamines; C048584:4-(carbethoxynitrosamino)-4-(3-pyridyl)butanal; C048585:4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine