Mutagenicity of aromatic amines and amides with chemical models for cytochrome P450 in Ames assay
| Autor: | Keiko Inami, Mikiko Okazawa, Masataka Mochizuki |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Salmonella typhimurium
Magnesium monoperoxyphthalate Toxicology medicine.disease_cause Ames test chemistry.chemical_compound Cytochrome P-450 Enzyme System medicine Organic chemistry Amines chemistry.chemical_classification Fluorenes biology Mutagenicity Tests Cytochrome P450 Aromatic amine General Medicine 2-Acetylaminofluorene Porphyrin Amides Benzidine chemistry Models Chemical biology.protein Genotoxicity Mutagens |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 23(6) |
| ISSN: | 1879-3177 |
| Popis: | Chemical models for cytochrome P450, consisting of water-insoluble or water-soluble iron porphyrin plus an oxidant, have been used to detect the mutagenicity of promutagens in genotoxicity assays. The procedure for using chemical models for cytochrome P450 as substitutes for the S9 mix in the Ames assay have been already established. Aromatic amines and amides require metabolic activation by cytochrome P450 when they exert their mutagenicity in Salmonella typhimurium strains. In this study, we optimized the conditions of the assay using a water-soluble chemical model, 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatoiron(III) pentachloride (4-MPy), plus tert-butyl hydroperoxide (t-BuOOH), magnesium monoperoxyphthalate, or iodosylbenzene, by comparing the mutagenicity of 2-aminofluorene (AF) in the Ames test. The model with 4-MPy/t-BuOOH showed the highest AF mutagenic potency. The chemical model activated 2-naphthylamine, 4-aminobiphenyl, and benzidine in S.typhimurium TA98. In aromatic amides, the model with 4-MPy/t-BuOOH weakly activated 2-acetylaminofluorene (AAF). To detect higher mutagenicity of aromatic amides, we used a higher concentration of 4-MPy/t-BuOOH by a factor of 5 over that used for aromatic amines, and then detected the mutagenicity of AAF, 2-acetylaminoanthracene, and 2-acetylamino-9-fluorenone. Furthermore, we concluded that the AAF mutagenicity in the presence of 4-MPy/t-BuOOH is derived from N-hydroxylacetylamino compounds. |
| Databáze: | OpenAIRE |
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