Genotoxicity but not the AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants.
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.
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Helena
H
Líbalová
Department of Chemistry, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
Simona
S
Krčková
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Kateřina
K
Uhlířová
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Alena
A
Milcová
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Jana
J
Schmuczerová
Department of Chemistry, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
Miroslav
M
Ciganek
Czech Technical University in Prague, Karlovo namesti 13, 121 35 Prague 2, Czech Republic.
Jiri
J
Kléma
Czech Technical University in Prague, Karlovo namesti 13, 121 35 Prague 2, Czech Republic.
Miroslav
M
Machala
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Radim J
RJ
Šrám
Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic. Electronic address: jtopinka@biomed.cas.cz.
Jan
J
Topinka
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000493:pharmacokinetics / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D018153:Czech Republic; D005449:Fluorenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009152:Mutagenicity Tests / Q000379:methods; D052638:Particulate Matter / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D045424:Complex Mixtures; D005449:Fluorenes; D052638:Particulate Matter; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D012313:RNA; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C022921:benzo(k)fluoranthene
Air pollution; Benzo[a]pyrene; Complex mixtures; DNA adducts; PAHs; PM2.5