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 |
|---|---|
| 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 |
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Keywords
- Ames assay
- Chemical model
- Cytochrome P450
- Metabolic activation
- Polyaromatic hydrocarbon
ASJC Scopus subject areas
- Environmental Chemistry
- Health, Toxicology and Mutagenesis
- Pollution
Cite this
Mutagenicity of polyaromatic hydrocarbons by chemical models for cytochrome P450 in Ames assay. / Inami, Keiko; Ishikawa, Satoko; Mochizuki, Masataka.
In: Toxicological and Environmental Chemistry, Vol. 92, No. 6, 07.2010, p. 1169-1176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutagenicity of polyaromatic hydrocarbons by chemical models for cytochrome P450 in Ames assay
AU - Inami, Keiko
AU - Ishikawa, Satoko
AU - Mochizuki, Masataka
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Ames assay
KW - Chemical model
KW - Cytochrome P450
KW - Metabolic activation
KW - Polyaromatic hydrocarbon
UR - http://www.scopus.com/inward/record.url?scp=77953119328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953119328&partnerID=8YFLogxK
U2 - 10.1080/02772240903266165
DO - 10.1080/02772240903266165
M3 - Article
AN - SCOPUS:77953119328
VL - 92
SP - 1169
EP - 1176
JO - Toxicological and Environmental Chemistry
JF - Toxicological and Environmental Chemistry
SN - 0277-2248
IS - 6
ER -