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

Genes and Environment

Hiroki Yasui¹  Keiko Inami¹  Masataka Mochizuki¹  Satoko Ishikawa²  Hirotaka Tsugumi² 

[1] Faculty of Pharmaceutical Sciences, Tokyo University of Science;Kyoritsu University of Pharmacy

关键词: N-alkyl-N-(3-carboxypropyl)nitrosamine;    chemical model;    BCPN;    metabolic activation;    urinary bladder carcinogen;   

DOI  :  10.3123/jemsge.2013.010

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(28)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. 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.

【 授权许可】

Unknown