Comparative mutagenicity of 4-(carbethoxynitrosamino)-4-(3-pyridyl)butanal and 4-(carbethoxynitrosamino)-1-(3-pyridy1)-1-butanone, model compounds for α-hydroxylation of N'-nitrosonornicotine

Abstract

4-(Carbethoxynitrosamino)-1-(3-pyridy1)butanal, a stable precursor to the putative diazohydroxide formed by 5'-hyd-roxylation 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-(carbethoxy-nitrosamino)-1-(3-pyridy)-1-butanone was a potent mutageon, but 4-(carbethoxynitrosamino)-1-(3-pyridy) 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'-nitrosonornocotine has higher inherent mutagemicity toward S. typhimurinum than does the corresponding diazohydroxide formed by 5'-hydroxylation.