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Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants
P. Rossner, A. Mrhalkova, K. Uhlirova, M. Spatova, A. Rossnerova, H. Libalova, J. Schmuczerova, A. Milcova, J. Topinka, RJ. Sram,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- DNA Adducts MeSH
- Cell Line MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Fibroblasts drug effects metabolism MeSH
- Air Pollutants chemistry toxicity MeSH
- Environmental Pollutants chemistry toxicity MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- DNA Repair * MeSH
- Particulate Matter chemistry toxicity MeSH
- Lung MeSH
- Polycyclic Aromatic Hydrocarbons chemistry toxicity MeSH
- Cell Proliferation drug effects MeSH
- Gene Expression Regulation drug effects MeSH
- Xeroderma Pigmentosum Group A Protein genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
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