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.

• Klíčová slova
• 1-nitropyrene, 3-nitrobenzanthrone, benzo[a]pyrene, bulky DNA adducts, gene expression, oxidative damage,
• 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
• hydroxysteroiddehydrogenasy 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
• Názvy látek
• 1-nitropyrene MeSH Prohlížeč
• 3-nitrobenzanthrone MeSH Prohlížeč
• adukty DNA MeSH
• AKR1C2 protein, human MeSH Prohlížeč
• benz(a)anthraceny MeSH
• benzopyren MeSH
• cyklooxygenasa 2 MeSH
• CYP1A1 protein, human MeSH Prohlížeč
• CYP1B1 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P450 CYP1B1 MeSH
• hydroxysteroiddehydrogenasy MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NQO1 protein, human MeSH Prohlížeč
• POR protein, human MeSH Prohlížeč
• PTGS2 protein, human MeSH Prohlížeč
• pyreny MeSH
• systém (enzymů) cytochromů P-450 MeSH
• výfukové emise vozidel MeSH