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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

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Mutagens
Salmonella typhimurium
Hydroxyl Radical
Oxides
Cytochrome P-450 Enzyme System
Alkyl and Aryl Transferases
Chemical Models
Nitrosamines
Salmonella
Alkylation
Nuclear magnetic resonance
Oxidation
Mutation
DNA
nitrosomethyl-N-butylamine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Pharmacology

Cite this

Structure and mutagenicity of a direct-acting mutagen derived from the reaction of N-nitroso-N-methylbutylamine with hydroxyl radical. / Inami, Keiko; Miura, Motofumi; Tsutsumi, Nozomi; Okochi, Eriko; Susaki, Yoko; Ishikawa, Satoko; Motohashi, Shigeyasu; Shiino, Junko; Takeda, Kei; Mochizuki, Masataka.

In: Heterocycles, Vol. 84, No. 2, 2012, p. 1081-1088.

Research output: Contribution to journalArticle

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, vol. 84, no. 2, pp. 1081-1088. https://doi.org/10.3987/COM-11-S(P)90
Inami, Keiko ; Miura, Motofumi ; Tsutsumi, Nozomi ; Okochi, Eriko ; Susaki, Yoko ; Ishikawa, Satoko ; Motohashi, Shigeyasu ; Shiino, Junko ; Takeda, Kei ; Mochizuki, Masataka. / Structure and mutagenicity of a direct-acting mutagen derived from the reaction of N-nitroso-N-methylbutylamine with hydroxyl radical. In: Heterocycles. 2012 ; Vol. 84, No. 2. pp. 1081-1088.
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