Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Prague, Czech Republic.
Toxicol Appl Pharmacol. 2010 Nov 1;248(3):194-200. doi: 10.1016/j.taap.2010.07.027. Epub 2010 Aug 6.
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.
DNA 单链断裂水平降低（反映 DNA 损伤）与苯乙烯暴露增加有关，而碱基切除修复能力则呈剂量依赖性增加。为了进一步阐明上述方面，我们调查了 71 名苯乙烯暴露工人和 51 名对照个体的 SSB、微核、DNA 修复能力和 XRCC1、hOGG1 和 XPC 基因的 mRNA 表达之间的相关性。工作场所和血液中的苯乙烯浓度分别反映了职业暴露和个体暴露。将工人分为低（<50mg/m³）和高（>50mg/m³）苯乙烯暴露组。通过彗星试验分析外周血淋巴细胞中的 DNA 损伤和 DNA 修复能力，通过 qPCR 确定 mRNA 表达水平。SSB 与工作场所苯乙烯浓度呈显著负相关（R=-0.38，p=0.001），男性 SSB 也明显较高（p=0.001）。低暴露组的修复辐射诱导的 DNA 损伤的能力最高（1.34±1.00 SSB/10⁹Da），其次是高暴露组（0.72±0.81 SSB/10⁹Da）和对照组（0.65±0.82 SSB/10⁹Da）。XRCC1、hOGG1 和 XPC 的 mRNA 表达水平与血液和工作场所中的苯乙烯浓度呈负相关（p<0.001），与 SSB 呈正相关（p<0.001）。微核不受苯乙烯暴露的影响，但在老年人和女性中较高（p<0.001）。在这项研究中，我们没有证实之前关于苯乙烯诱导的遗传毒性增加 DNA 修复反应的发现。然而，SSB 和 XRCC1、hOGG1 和 XPC 的 mRNA 表达水平与苯乙烯暴露呈负相关，这需要进一步进行针对性更强的研究。
