Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549) |
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Authors: | Pavel Rossner Jr Simona Strapacova Jitka Stolcpartova Jana Schmuczerova Alena Milcova Jiri Neca Veronika Vlkova Tana Brzicova Miroslav Machala Jan Topinka |
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Affiliation: | 1Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic; (J.St.); (J.Sc.); (A.M.); (V.V.); (T.B.); (J.T.);2Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic; (S.S.); (J.N.); (M.M.);3Institute for Environmental Studies, Faculty of Science, Charles University, Benatska 2, 128 01 Prague 2, Czech Republic |
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Abstract: | We investigated the toxicity of benzoa]pyrene (Ba]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: Ba]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 Ba]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. |
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Keywords: | benzo[a]pyrene 1-nitropyrene 3-nitrobenzanthrone bulky DNA adducts oxidative damage gene expression |
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