Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy.
PLoS One. 2013 Sep 23;8(9):e75401. doi: 10.1371/journal.pone.0075401. eCollection 2013.
The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting.
Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure.
Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis.
The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.
本研究旨在评估一组参与毒理学的基因在低于职业标准设定的水平下暴露于苯乙烯时的表达情况。
对玻璃纤维船业工人进行了一组与应激和毒性相关的基因评估，并与与肝损伤相关的生化参数相关联。使用受试者的尿液中苯乙烯代谢物（MA+PGA）和工作场所空气中收集的环境采样数据来估计苯乙烯暴露量。
表达谱分析显示，在苯乙烯暴露组中，编码应激反应蛋白（HSPA1L、EGR1、IL-6、IL-1β、TNSF10 和 TNFα）的基因大量上调；在血清中进一步证实了细胞因子的释放。然后根据苯乙烯暴露水平对暴露工人进行分层。即使在低水平下，EGR1 基因的上调也与 IL-6、TNSF10 和 TNFα 的表达和转录蛋白水平平行，这在苯乙烯暴露工人中观察到 EGR1 途径的激活与高暴露受试者中发现的轻微肝标志物增加有关，尽管它们仍在正常范围内。ALT 和 AST 水平不受饮酒影响，并通过多元回归分析与尿中苯乙烯代谢物呈正相关。
促炎细胞因子 IL-6 和 TNFα 是参与肝损伤反应和再生的过程的主要介质。在这里，我们表明苯乙烯在低暴露下诱导涉及细胞保护和细胞毒性的应激反应基因，在高暴露下导致轻度亚临床肝毒性。
