Ruthenium porphyrin and oxidant convert N-nitrosodialkylamines into direct-acting mutagen in the Ames assay

Inami, Keiko; Yoshimitsu, Kyohei; Seino, Hideaki; Mochizuki, Masahito

doi:10.1039/c3tx50036e

Cited by 3 publications

(1 citation statement)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we applied a chemical model for cytochrome P450 as an alternative for metabolic activation to the Ames assay (7,8). Previous reports have shown that the chemical models consisting of iron porphyrin or ruthenium porphyrin plus an oxidant have induced mutagenicity in aromatic amines, heterocyclic amines, polyaromatic hydrocarbons, and N-nitrosodialkylamines in Salmonella strains (20)(21)(22)(23). The 4-MPy plus t-BuOOH system activated MCPN, ECPN, PCPN and BCPN into direct-acting mutagens.…”

Section: Discussionmentioning

confidence: 99%

Oxidation of N-Alkyl-N-(3-carboxypropyl)nitrosamines by Iron Porphyrin and Oxidant Forms Alkylating Mutagens

Inami

Yasui

Tsugumi

et al. 2013

Genes and Environment

Self Cite

View full text Add to dashboard Cite

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(1methylpyridinium-4-yl)porphyrinatoiron(III) pentachloride (4-MPy) plus an oxidant. The N-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 and t-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.

show abstract