Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers |
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Authors: | Monika Hanova Rudolf Stetina Radka Vaclavikova Zdenek Smerhovsky Alessio Naccarati Pavel Soucek Paola Manini Kari Hemminki |
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Affiliation: | a Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Prague, Czech Republicb Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republicc Purkynje Military Medical Academy, Hradec Kralove, Czech Republicd National Inst. Public Health, Prague, Czech Republice Dept. Occup. Medicine at Regional Hygiene Station, Hradec Kralove, Czech Republicf 2nd Medical Faculty, Charles University, Prague, Czech Republicg Res. Base, Slovak Medical Univ., Bratislava, Slovak Republich Dept. of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Italyi German Cancer Research Center (Deutsches Krebs Forschungs Zentrum; DKFZ), Heidelberg, Germany |
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Abstract: | Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure. The workers were divided into low (below 50 mg/m3) and high (above 50 mg/m3) styrene exposure groups. DNA damage and DNA repair capacity were analyzed in peripheral blood lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A significant negative correlation was observed between SSBs and styrene concentration at workplace (R = − 0.38, p = 0.001); SSBs were also significantly higher in men (p = 0.001). The capacity to repair irradiation-induced DNA damage was the highest in the low exposure group (1.34 ± 1.00 SSB/109 Da), followed by high exposure group (0.72 ± 0.81 SSB/109 Da) and controls (0.65 ± 0.82 SSB/109 Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated with styrene concentrations in blood and at workplace (p < 0.001) and positively with SSBs (p < 0.001). Micronuclei were not affected by styrene exposure, but were higher in older persons and in women (p < 0.001). In this study, we did not confirm previous findings on an increased DNA repair response to styrene-induced genotoxicity. However, negative correlations of SSBs and mRNA expression levels of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted study. |
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Keywords: | SO, Styrene-7,8-oxide BER, Base-excision repair PBL, Peripheral blood lymphocytes Da, Daltons γ-irradiation, Gamma irradiation EndoIII sites, SSBs endonuclease III sites MN, Micronuclei XRCC1, X-ray repair cross-complementing protein 1 hOGG1, 8-hydroxyguanine DNA glycosylase XPC, Xeroderma pigmentosum, complementation group C SSB, Single-strand breaks bp, Base pair B2M, Beta-2-Microglobulin GAPDH, Glyceraldehyde-3-phosphate dehydrogenase PPIA, Peptidylprolyl isomerase A (cyclophilin A) qPCR, Quantitative PCR SD, Standard deviation |
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