Mutagenicity of Heterocyclic Amines by Biomimetic Chemical Models for Cytochrome P450 in Ames Assay

Genes and Environment

Keiko Inami¹  Minako Nagao¹  Masataka Mochizuki¹  Satoko Ishikawa¹ 

[1] Kyoritsu University of Pharmacy

关键词: iron porphyrin;    chemical model;    cytochrome P450;    metabolic activation;    heterocyclic amine;   

DOI  :  10.3123/jemsge.32.7

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(43)Cited-By(2)Heterocyclic amines (HCAs) are a family of mutagenic and carcinogenic compounds produced during cooking or other burning processes, and exist in the environment. HCAs are metabolically activated by cytochrome P450, conjugated by phase II enzymes, to react with guanine bases. The aim of this study is to establish a chemical model for cytochrome P450 as an alternative to S-9 mix for detecting HCA mutagenicity in Salmonella strain. A chemical model was developed by comparing the mutagenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in the presence of an iron porphyrin and an oxidant. The iron porphyrin derivatives, water-soluble 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatoiron (III) chloride (4-MPy) or water-insoluble 5,10,15,20-tetrakis (pentafluorophenyl)porphyrinatoiron (III) chloride (F5P), and the oxidant tert-butyl hydroperoxide (t-BuOOH), magnesium monoperoxyphthalate or iodosylbenzene were used. 4-MPy or F5P with t-BuOOH activated Trp-P-2, and the activity was similar with either porphyrin. Water-soluble model has a better chance to detect unstable compound, since the tester strain was exposed in the whole incubation period in the mutation procedure with 4-MPy. The effectiveness of 4-MPy/t-BuOOH was evaluated with other HCAs; IQ, MeIQ, MeIQx, Glu-P-1, Glu-P-2, PhIP, Trp-P-1, MeAαC and AαC. All HCAs except for MeAαC and AαC were mutagenic in Salmonella typhimurium TA1538. MeAαC and AαC were not mutagenic in TA1538, but they were mutagenic in S. typhimurium TA1538/pYG219, which overexpresses O-acetyltranferase on the TA1538 genetic background. Although the HCAs mutagenicity with the chemical model was weaker than that with S-9 mix, the chemical models activated HCAs without S-9 mix in the Ames assay.

【 授权许可】

Unknown