砷冶炼厂工人砷甲基化代谢与肝和皮肤损伤及LncRNAs表达的关系

Relationship of arsenic methylation metabolism with liver and skin damage and expressions of long non-coding RNAs in arsenic smeltery workers

[目的]探讨职业性砷接触工人砷甲基化代谢转化模式与肝和皮肤损伤、长链非编码RNA(LncRNAs)表达的关系。[方法]2013年10月选择云南省文山州两个砷冶炼厂的112名工人作为接触组,无砷接触经历的居民41人为对照组。对接触组进行健康监护体检,检查肝和皮肤损伤情况并分为4组(无损伤组、肝损伤组、皮肤损伤组、肝和皮肤均损伤组);用带有砷预处理系统的原子吸收分光光度计检测尿中无机砷、甲基砷酸和二甲基砷酸含量,并计算一、二级甲基化指数;用实时荧光定量PCR法检测外周血3种与恶性肿瘤发生关系相关的LncRNAs(MEG3、TUG1和HOTAIR)表达。[结果]职业性砷接触工人年龄(33.9±16.8)岁,工龄(16.6±9.7)月,其中无损伤组42人,肝损伤组29人,皮肤损伤组21人,肝和皮肤均损伤组20人。各接触组尿中3种砷化合物浓度均高于对照组(均P<0.05),一、二级甲基化指数低于对照组(均P<0.05);肝损伤组一级甲基化指数和皮肤损伤组一、二级甲基化指数低于肝和皮肤均损伤组(P<0.05)。与对照组相比,无损伤、皮肤损伤、肝和皮肤均损伤组外周血MEG3和HOTAIR表达升高,无损伤、肝和皮肤均损伤组工人TUG1表达升高(P<0.05)。与肝和皮肤均损伤组比较,无损伤和肝损伤组MEG3表达降低,肝损伤组TUG1和HOTAIR表达降低(P<0.05)。[结论]职业砷接触工人不同砷甲基化代谢模式与肝和皮肤损伤、外周血LncRNAs表达之间存在关联。

[Objective] To assess the relationship of arsenic methylation metabolism with liver and skin damage and expressions of long non- coding RNAs in arsenic smeltery workers. [Methods] Workers exposed to arsenic （n=112） from two arsenic smelteries in Wenshan of Yunnan Province and control individuals without arsenic exposure （n=41） were selected in October 2013. After medical examinations, the arsenic exposed participants were divided into four groups （without damage, with liver damage, with skin damage, with both liver and skin damage）. Inorganic arsenic （iAs）, methylarsonic acid （MMA）, and dimethylarsinic acid （DMA） in urine were determined using atomic absorption spectrophotometer with an arsenic speciation pretreatment system. Primary methylation index （PMI） and secondary methylation index （SMI） were calculated. Real-time fluorescence quantitative PCR was performed to detect the expressions of three long non-coding RNAs （MEG3, TUG1, and HOTAIR） in peripheral blood closely related to malignant tumor.[Results] The mean age of the arsenic exposed workers was （33.9 ±16.8） years, and the mean length of service was （16.6 ± 9.7） months. There were 42 workers without damage, 29 with liver damage, 21 with skin damage, and 20 with both liver and skin damage. Compared to the control group, the concentrations of three arsenic species were all higher （Ps 〈 0.05）, and PMI ＆ SMI were lower （Ps 〈 0.05） in the workers exposed to arsenic. Compared to the workers with both liver and skin damage, PMI in the workers with liver damage as well as PMI and SMI in the workers with skin damage were lower （Ps 〈 0.05）. Compared to the control group, the expressions of MEG3 and HOTAIR in peripheral blood were higher in the workers without damage, with skin damage, and with both liver and skin damage, and the expressions of TUG1 were higher in the workers without damage and with both liver and skin damage （Ps 〈 0.05）. Compared to the workers with both liver and skin damage, the expressions of MEG3 were lower in the workers without damage and with liver damage, and the expressions of TUG1 and HOTAIR were lower in the workers with liver damage （P〈0.05）. [Conclusion] There is a correlation of arsenic methylation metabolism with liver and skin damage and expressions of long non- coding RNAs in arsenic exposed workers.