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, Masataka Mochizuki

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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 Fe 2+-Cu 2+-H 2O 2, 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 Fe 2+-Cu 2+-H 2O 2 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 Fe 2+-Cu 2+-H 2O 2 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 O 6-alkylguanine alkyltransferase, was higher than that in the parent strain S. typhimurium TA1535, indicating that the mutations are caused by DNA alkylation.

Original languageEnglish
Pages (from-to)1081-1088
Number of pages8
JournalHeterocycles
Volume84
Issue number2
DOIs
Publication statusPublished - 2012 Feb 7

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ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

Cite this

Inami, K., Miura, M., Tsutsumi, N., Okochi, E., Susaki, Y., Ishikawa, S., Motohashi, S., Shiino, J., Takeda, K., & Mochizuki, M. (2012). Structure and mutagenicity of a direct-acting mutagen derived from the reaction of N-nitroso-N-methylbutylamine with hydroxyl radical. Heterocycles, 84(2), 1081-1088. https://doi.org/10.3987/COM-11-S(P)90