Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.

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...

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Main Authors: Pavel Rossner, Andrea Mrhalkova, Katerina Uhlirova, Milada Spatova, Andrea Rossnerova, Helena Libalova, Jana Schmuczerova, Alena Milcova, Jan Topinka, Radim J Sram
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3716811?pdf=render
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author Pavel Rossner
Andrea Mrhalkova
Katerina Uhlirova
Milada Spatova
Andrea Rossnerova
Helena Libalova
Jana Schmuczerova
Alena Milcova
Jan Topinka
Radim J Sram
author_facet Pavel Rossner
Andrea Mrhalkova
Katerina Uhlirova
Milada Spatova
Andrea Rossnerova
Helena Libalova
Jana Schmuczerova
Alena Milcova
Jan Topinka
Radim J Sram
author_sort Pavel Rossner
collection DOAJ
description 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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spelling doaj.art-aae2bc8863c24f0e947e013f94266c572022-12-22T01:19:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6919710.1371/journal.pone.0069197Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.Pavel RossnerAndrea MrhalkovaKaterina UhlirovaMilada SpatovaAndrea RossnerovaHelena LibalovaJana SchmuczerovaAlena MilcovaJan TopinkaRadim J SramThe 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.http://europepmc.org/articles/PMC3716811?pdf=render
spellingShingle Pavel Rossner
Andrea Mrhalkova
Katerina Uhlirova
Milada Spatova
Andrea Rossnerova
Helena Libalova
Jana Schmuczerova
Alena Milcova
Jan Topinka
Radim J Sram
Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
PLoS ONE
title Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
title_full Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
title_fullStr Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
title_full_unstemmed Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
title_short Nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants.
title_sort nucleotide excision repair is not induced in human embryonic lung fibroblasts treated with environmental pollutants
url http://europepmc.org/articles/PMC3716811?pdf=render
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