title: Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549).
abstract: We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM), 1-NP (1 and 10 μM) and 3-NBA (0.5 and 5 μM). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH) nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. prossner@biomed.cas.cz.
authors: Pavel
authors: P
authors: Rossner
authors: Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic. strapacova@vri.cz.
authors: Simona
authors: S
authors: Strapacova
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. jitka.stolcpartova@biomed.cas.cz.|Institute for Environmental Studies, Faculty of Science, Charles University, Benatska 2, 128 01 Prague 2, Czech Republic. jitka.stolcpartova@biomed.cas.cz.
authors: Jitka
authors: J
authors: Stolcpartova
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. schmucze@yahoo.com.
authors: Jana
authors: J
authors: Schmuczerova
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. milcova@biomed.cas.cz.
authors: Alena
authors: A
authors: Milcova
authors: Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic. neca@vri.cz.
authors: Jiri
authors: J
authors: Neca
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. veronika.vlkova@biomed.cas.cz.
authors: Veronika
authors: V
authors: Vlkova
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. tana.brzicova@biomed.cas.cz.
authors: Tana
authors: T
authors: Brzicova
authors: Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic. machala@vri.cz.
authors: Miroslav
authors: M
authors: Machala
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic. jtopinka@biomed.cas.cz.
authors: Jan
authors: J
authors: Topinka
mesh_terms: D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D001551:Benz(a)Anthracenes / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D011721:Pyrenes / Q000633:toxicity; D001335:Vehicle Emissions / Q000633:toxicity*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D001551:Benz(a)Anthracenes; D001564:Benzo(a)pyrene; D051546:Cyclooxygenase 2; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D018736:DNA Adducts; D006913:Hydroxysteroid Dehydrogenases; D016660:NAD(P)H Dehydrogenase (Quinone); D011721:Pyrenes; D001335:Vehicle Emissions; C000602470:POR protein, human; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; C496540:PTGS2 protein, human; C447479:NQO1 protein, human; C117220:3-nitrobenzanthrone; C032668:1-nitropyrene
keywords: 1-nitropyrene; 3-nitrobenzanthrone; benzo[a]pyrene; bulky DNA adducts; gene expression; oxidative damage