Genotoxicity but not the AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
24472612
DOI
10.1016/j.toxlet.2014.01.028
PII: S0378-4274(14)00039-3
Knihovny.cz E-resources
- Keywords
- Air pollution, Benzo[a]pyrene, Complex mixtures, DNA adducts, PAHs, PM2.5,
- MeSH
- Aryl Hydrocarbon Hydroxylases genetics metabolism MeSH
- Benzo(a)pyrene chemistry pharmacokinetics toxicity MeSH
- Cytochrome P-450 CYP1A1 genetics metabolism MeSH
- Cytochrome P-450 CYP1B1 MeSH
- Fluorenes chemistry pharmacokinetics toxicity MeSH
- Complex Mixtures pharmacokinetics toxicity MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Particulate Matter chemistry pharmacokinetics toxicity MeSH
- Lung drug effects enzymology metabolism physiology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Receptors, Aryl Hydrocarbon genetics metabolism MeSH
- Gene Expression Regulation, Enzymologic drug effects MeSH
- RNA chemistry genetics MeSH
- Mutagenicity Tests methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Aryl Hydrocarbon Hydroxylases MeSH
- benzo(k)fluoranthene MeSH Browser
- Benzo(a)pyrene MeSH
- CYP1A1 protein, human MeSH Browser
- CYP1B1 protein, human MeSH Browser
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1B1 MeSH
- Fluorenes MeSH
- Complex Mixtures MeSH
- Particulate Matter MeSH
- Receptors, Aryl Hydrocarbon MeSH
- RNA MeSH
In this study, we compared the genotoxicity and aryl hydrocarbon receptor (AhR)-dependent transcriptional changes of selected target genes in human lung epithelial A549 cells incubated for 24 h, either with extractable organic matter (EOMs) from airborne particles <2.5 μm (PM2.5) collected at four localities from heavily polluted areas of the Czech Republic or two representative toxic polycyclic aromatic hydrocarbons (PAHs) present in EOMs, benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F). Genotoxic effects were determined using DNA adduct analysis or analysis of expression of selected AhR-related genes involved in bioactivation of PAHs (CYP1A1, CYP1B1) and transcriptional repression (TIPARP). Sampled localities differing in the extent and source of air pollution did not exhibit substantially different genotoxicity. DNA adduct levels induced by three subtoxic EOM concentrations were relatively low (1-5 adducts/10(8) nucleotides), compared to levels induced by similar concentrations of B[a]P, while B[k]F gave very low DNA adduct levels. Here, we compared genotoxicity and gene deregulation induced by complex mixtures containing PAHs with the effects of the comparable concentrations of individual PAHs. Our results suggested inhibition of formation of B[a]P-induced DNA adducts compared to individual B[a]P, probably attributable to competitive inhibition by other non-genotoxic EOM components. In contrast, induction of AhR target genes appeared not to be antagonized by the components of complex mixtures, as induction of CYP1A1, CYP1B1 and TIPARP transcripts reached maximum levels induced by PAHs.
Czech Technical University Prague Karlovo namesti 13 121 35 Prague 2 Czech Republic
Department of Chemistry Veterinary Research Institute Hudcova 296 70 621 00 Brno Czech Republic
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