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Genotoxicant exposure, activation of the aryl hydrocarbon receptor, and lipid peroxidation in cultured human alveolar type II A549 cells
P. Rossner, H. Libalova, K. Vrbova, T. Cervena, A. Rossnerova, F. Elzeinova, A. Milcova, Z. Novakova, J. Topinka,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Benz(a)Anthracenes toxicity MeSH
- Benzo(a)pyrene toxicity MeSH
- A549 Cells MeSH
- Cyclooxygenase 1 metabolism MeSH
- Cytochrome P-450 CYP1A1 metabolism MeSH
- Humans MeSH
- Mutagens toxicity MeSH
- Cell Line, Tumor MeSH
- NF-kappa B metabolism MeSH
- Lipid Peroxidation drug effects MeSH
- Particulate Matter toxicity MeSH
- Alveolar Epithelial Cells drug effects MeSH
- Polycyclic Aromatic Hydrocarbons toxicity MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Basic Helix-Loop-Helix Transcription Factors metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.
References provided by Crossref.org
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- $a The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.
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- $a Libalova, Helena $u Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20, Prague, Czech Republic; Biology Center of the Czech Academy of Sciences, Institute of Entomology, Ceske Budejovice, Czech Republic. Electronic address: helena.libalova@iem.cas.cz.
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- $a Elzeinova, Fatima $u Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20, Prague, Czech Republic. Electronic address: fatima.elzeinova@iem.cas.cz.
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- $a Novakova, Zuzana $u Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20, Prague, Czech Republic. Electronic address: zuzana.novakova@iem.cas.cz.
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- $a Topinka, Jan $u Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the CAS, Videnska 1083, 142 20, Prague, Czech Republic. Electronic address: jan.topinka@iem.cas.cz.
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