Oxidation of n-alkyl-n-(3-carboxypropyl)nitrosamines by iron porphyrin and oxidant forms alkylating mutagens

Keiko Inami, Hiroki Yasui, Hirotaka Tsugumi, Satoko Ishikawa, Masataka Mochizuki

Research output: Contribution to journalArticle

Abstract

N-Alkyl-N-(3-carboxypropyl)nitrosamines are known to selectively induce urinary bladder tumor in rats and mice. To detect DNA damage by N-alkyl-N-(3-carboxypropyl)- nitrosamines, we evaluated their mutagenicity using the Ames assay in S. typhimurium and E. coli under oxidative conditions of chemical model for cytochrome P450. The activation system consisted of 5,10,15,20-tetrakis(1- methylpyridinium-4-yl)porphyrinatoiron(III) pentachloride (4-MPy) plus an oxidant. TheN-alkyl-N-(3-carboxypropyl)- nitrosamines; N-methyl-N-(3-carboxypropyl)nitrosamine (MCPN), N-ethyl-N-(3-carboxypropyl) nitrosamine (ECPN), N-propyl-N-(3-carboxypropyl)nitrosamine (PCPN),N-butyl- N-(3-carboxypropyl)nitrosamine (BCPN), were treated with 4-MPy andt-BuOOH in acetonitrile for 30 min at room temperature, the reaction mixture was extracted with dichloromethane, and the organic phase was assayed for their mutagenicity in Salmonella typhimurium TA1535 and Escherichia coli WP2 uvrA. The dichloromethane extract derived from the reaction mixture of MCPN, ECPN, PCPN or BCPN with 4-MPy plus t-BuOOH was mutagenic in both of the strains, indicating that N-alkyl-N-(3-carboxypropyl) nitrosamines were oxidized to direct-acting mutagens by the 4-MPy plus t-BuOOH. The mutagenicity of oxidized BCPN extract in S. typhimurium YG7108 was higher than that in S. typhimurium TA1535, suggesting that the mutagenicity derived from BCPN was due to DNA alkylation. Furthermore, the DNA seemed to be butylated, not 3-carboxypropylated, exerting the mutagenicity of BCPN in the presence of 4-MPy and t-BuOOH.

Original languageEnglish
Pages (from-to)99-104
Number of pages6
JournalGenes and Environment
Volume35
Issue number4
DOIs
Publication statusPublished - 2013 Dec 19

Keywords

  • BCPN
  • Chemical model
  • Metabolic activation
  • N-alkyl-N-(3-carboxypropyl)nitrosamine
  • Urinary bladder carcinogen

ASJC Scopus subject areas

  • Social Psychology
  • Genetics
  • Environmental Science (miscellaneous)

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