The cellular response to genotoxic treatment depends on the cell line used. Although tumor cell lines are widely used for genotoxicity tests, the interpretation of the results may be potentially hampered by changes in cellular processes caused by malignant transformation. In our study we used normal human embryonic lung fibroblasts (HEL12469 cells) and tested their response to treatment with benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5 µm (PM2.5) collected in two Czech cities differing in levels and sources of air pollution. We analyzed multiple endpoints associated with exposure to polycyclic aromatic hydrocarbons (PAHs) including the levels of bulky DNA adducts and the nucleotide excision repair (NER) response [expression of XPE, XPC and XPA genes on the level of mRNA and proteins, unscheduled DNA synthesis (UDS)]. EOMs were collected in the winter and summer of 2011 in two Czech cities with different levels and sources of air pollution. The effects of the studied compounds were analyzed in the presence (+S9) and absence (-S9) of the rat liver microsomal S9 fraction. The levels of bulky DNA adducts were highest after treatment with B[a]P, followed by winter EOMs; their induction by summer EOMs was weak. The induction of both mRNA and protein expression was observed, with the most pronounced effects after treatment with B[a]P (-S9); the response induced by EOMs from both cities and seasons was substantially weaker. The expression of DNA repair genes was not accompanied by the induction of UDS activity. In summary, our results indicate that the tested compounds induced low levels of DNA damage and affected the expression of NER genes; however, nucleotide excision repair was not induced.

• MeSH
• adukty DNA MeSH
• buněčné linie MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• látky znečišťující vzduch chemie   toxicita   MeSH
• látky znečišťující životní prostředí chemie   toxicita   MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• oprava DNA * MeSH
• pevné částice chemie   toxicita   MeSH
• plíce MeSH
• polycyklické aromatické uhlovodíky chemie   toxicita   MeSH
• proliferace buněk účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• xeroderma pigmentosum - protein skupiny A genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• DNA vazebné proteiny MeSH
• látky znečišťující vzduch MeSH
• látky znečišťující životní prostředí MeSH
• messenger RNA MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• xeroderma pigmentosum - protein skupiny A MeSH
• XPA protein, human MeSH Prohlížeč
• XPC protein, human MeSH Prohlížeč

The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons adsorbed onto respirable air particles (PM2.5, diameter < 2.5 μm) on DNA adducts and chromosomal aberrations was repeatedly studied in Prague, Czech Republic, in groups of policemen working in the downtown area and in bus drivers. Personal exposure was evaluated using personal samplers during working shifts. DNA adducts were analyzed in lymphocytes by the (32)P-postlabeling assay and chromosomal aberrations were analyzed by conventional cytogenetic analysis and fluorescent in situ hybridization (FISH). The impact of environmental pollution on DNA adducts and chromosomal aberrations was studied in a total of 950 subjects. Our results suggest that the environmental exposure of nonsmokers to concentrations higher than 1 ng benzo[a]pyrene/m(3) represents a risk of DNA damage, as indicated by an increase in DNA adducts and the genomic frequency of translocations determined by FISH.

• Publikační typ
• časopisecké články MeSH