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.
- MeSH
- adukty DNA účinky léků genetika MeSH
- benz(a)anthraceny toxicita MeSH
- benzopyren toxicita MeSH
- buňky A549 MeSH
- cyklooxygenasa 2 genetika MeSH
- cytochrom P-450 CYP1A1 genetika MeSH
- cytochrom P450 CYP1B1 genetika MeSH
- hydroxysteroidní dehydrogenasy genetika MeSH
- lidé MeSH
- NAD(P)H dehydrogenasa (chinon) genetika MeSH
- pneumocyty účinky léků metabolismus MeSH
- poškození DNA účinky léků genetika MeSH
- pyreny toxicita MeSH
- systém (enzymů) cytochromů P-450 genetika MeSH
- výfukové emise vozidel toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This study quantified the temporal variability of concentration of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), genotoxicity, oxidative DNA damage and dioxin-like activity of the extractable organic matter (EOM) of atmospheric aerosol particles of aerodynamic diameter (dae, μm) coarse (1 < dae < 10), upper- (0.5 < dae < 1) and lower-accumulation (0.17 < dae < 0.5) and ultrafine (<0.17) fractions. The upper accumulation fraction formed most of the aerosol mass for 22 of the 26 study days and contained ∼44% of total c-PAHs, while the ultrafine fraction contained only ∼11%. DNA adduct levels suggested a crucial contribution of c-PAHs bound to the upper accumulation fraction. The dioxin-like activity was also driven primarily by c-PAH concentrations. In contrast, oxidative DNA damage was not related to c-PAHs, as a negative correlation with c-PAHs was observed. These results suggest that genotoxicity and dioxin-like activity are the major toxic effects of organic compounds bound to size segregated aerosol, while oxidative DNA damage is not induced by EOM.
- MeSH
- adukty DNA analýza chemie MeSH
- aerosoly MeSH
- DNA chemie MeSH
- látky znečišťující vzduch analýza toxicita MeSH
- monitorování životního prostředí metody MeSH
- oxidace-redukce MeSH
- pevné částice analýza toxicita MeSH
- polycyklické aromatické uhlovodíky analýza toxicita MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
