Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers

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• 作者：Monika Hanova ; Rudolf Stetina ; Ludmila Vodickova ; Radka Vaclavikova ; Pavel Hlavac ; Zdenek Smerhovsky ; Alessio Naccarati ; Veronika Polakova ; Pavel Soucek ; Miroslava Kuricova ; Paola Manini ; Rajiv Kumar
• 关键词：Styrene exposure ; Genotoxicity ; DNA repair ; DNA repair rates ; Gene expression
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2010
• 出版时间：1 November 2010
• 年：2010
• 卷：248
• 期：3
• 页码：194-200
• 全文大小：286 K

文摘

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.