Abstract
DNA damage is an important step in carcinogenesis. The Ames assay is a short-term screening of carcinogens that induce DNA damage. Most carcinogens require enzymatic activation through oxidation by cytochrome P450 (CYP450) in the presence of S9 mix. A combination of iron (Fe)(III) porphyrin and an oxidant is also able to oxidize compounds as an alternative metabolic pathway to CYP450. Previously it was reported that a chemical model containing a water-soluble 5,10,15,20-tetrakis(1-methylpyridinium4-yl)porphyrinatoiron(III) chloride (4-MPy) and tert-butyl hydroperoxide (t-BuOOH) activated aromatic amines and amides. In this study, a chemical model composed of an Fe porphyrin, water-insoluble 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride (F5P) or water-soluble 4-MPy was optimized with an oxidant - t-BuOOH, magnesium monoperoxyphthalate (MPPT), or iodosylbenzene (PhIO). Subsequently the mutagenicity of benzo[a]pyrene (B[a]P) and chrysene in Salmonella typhimurium TA strains was compared. B[a]P was activated by a combination of F5P or 4-MPy plus MPPT or PhIO in S. typhimurium TA1538. The B[a]P-induced mutagenicity with F5P plus oxidant was higher than 4-MPy plus oxidant. Mutagenicity of chrysene, a tetracyclic aromatic hydrocarbon, was not detected in the presence of F5P/PhIO in S. typhimurium TA98, but was activated in the presence of F5P/MPPT. The F5P/MPPT activated other polyaromatic hydrocarbons (PAH) in the S. typhimurium TA98 assay including dibenz[a,c]anthracene, dibenz[a,h]anthracene, 3-methylcholanthrene, and benzo[a]anthracene. The results indicated that the F5P/MPPT was the most efficient model for detecting PAH-induced mutagenicity in the Ames assay.
Original language | English |
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Pages (from-to) | 1169-1176 |
Number of pages | 8 |
Journal | Toxicological and Environmental Chemistry |
Volume | 92 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2010 Jul 1 |
Keywords
- Ames assay
- Chemical model
- Cytochrome P450
- Metabolic activation
- Polyaromatic hydrocarbon
ASJC Scopus subject areas
- Environmental Chemistry
- Pollution
- Health, Toxicology and Mutagenesis