title: The aryl hydrocarbon receptor-mediated and genotoxic effects of fractionated extract of standard reference diesel exhaust particle material in pulmonary, liver and prostate cells.
abstract: Diesel exhaust particles (DEP) and the associated complex mixtures of organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), or their derivatives, have been suggested to exert deleterious effects on human health. We used a set of defined cellular models representing liver, lung and prostate tissues, in order to compare non-genotoxic and genotoxic effects of crude and fractionated extract of a standard reference DEP material - SRM 1650b. We focused on the aryl hydrocarbon receptor (AhR)-mediated activity, modulation of cell proliferation, formation of DNA adducts, oxidative DNA damage, and induction of DNA damage responses, including evaluation of apoptosis, and phosphorylation of p53 tumor suppressor and checkpoint kinases (Chk). Both PAHs and the polar aromatic compounds contributed to the AhR-mediated activity of DEP-associated organic pollutants. The principal identified AhR agonists included benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene, chrysene and several non-priority PAHs, including benzochrysenes and methylated PAHs. In contrast to PAHs, polar compounds contributed more significantly to overall formation of DNA adducts associated with phosphorylation of p53, Chk1 or Chk2, and partly with apoptosis. Therefore, more attention should be paid to identification of DEP-associated polar organic compounds, contributing to the AhR activation and cytotoxic/genotoxic effects of complex airborne mixtures of organic contaminants produced by diesel engines.
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Pálková
authors.affiliation: Department of Cytokinetics, Královopolská 135, Institute of Biophysics AS CR, 61265 Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Vondráček
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Trilecová
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Ciganek
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Pěnčíková
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Neča
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Vídeňská 1083, 14220 Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Milcová
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Vídeňská 1083, 14220 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Topinka
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic. Electronic address: machala@vri.cz.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Machala
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D018736:DNA Adducts; D004249:DNA Damage; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D052638:Particulate Matter / Q000633:toxicity*; D011467:Prostate / Q000473:pathology*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts; D009153:Mutagens; D052638:Particulate Matter; D018336:Receptors, Aryl Hydrocarbon; D001335:Vehicle Emissions
keywords: Air pollution; Apoptosis; Cell proliferation; DNA damage response; PAHs; SRM 1650b