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Paper | Special issue | Vol 84, No. 2, 2012, pp.1081-1088
Published online, 9th September, 2011
DOI: 10.3987/COM-11-S(P)90
Structure and Mutagenicity of a Direct-Acting Mutagen Derived from the Reaction of N-Nitroso-N-methylbutylamine with Hydroxyl Radical

Keiko Inami, Motofumi Miura, Nozomi Tsutsumi, Eriko Okochi, Yoko Susaki, Satoko Ishikawa, Shigeyasu Motohashi, Junko Shiino, Kei Takeda, and Masataka Mochizuki*

*Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510,

Abstract

The mutagenicity of N-nitrosamines is usually detected in the presence of an S9 mix, which includes cytochrome P450. The mutagenicity of N-nitrosodialkylamines is induced by Fe2+-Cu2+-H2O2, which can be used as a chemical model for cytochrome P450. However, a direct-acting mutagen derived from N-nitroso-N-methylbutylamine (NMB) by the same oxidation system has not been reported. In this study, we determined the structure of a direct-acting mutagen obtained from the reaction of NMB with Fe2+-Cu2+-H2O2 by comparing its instrumental data (1H, 13C NMR and IR) with that from the synthesized compound. We confirmed that the direct-acting mutagen derived from NMB with Fe2+-Cu2+-H2O2 was 5-methyl-5-nitro-1-pyrazoline 1-oxide. Furthermore, we investigated the mechanism of the mutagenicity by 5-methyl-5-nitro-1-pyrazoline 1-oxide using Salmonella typhimurium strains. The mutagenicity of 5-methyl-5-nitro-1-pyrazoline 1-oxide in S. typhimurium YG7108, which is deficient O6-alkylguanine alkyltransferase, was higher than that in the parent strain S. typhimurium TA1535, indicating that the mutations are caused by DNA alkylation.