Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, China.
Xinxiang Center for Disease Control and Prevention, Xinxiang, China.
PLoS One. 2019 Aug 5;14(8):e0220500. doi: 10.1371/journal.pone.0220500. eCollection 2019.
Aberrant DNA methylation patterns are common in cancers and environmental pollutant exposed subjects. Up to date, few studies have examined the aberrant DNA methylation patterns in benzene exposed workers. We recruited 141 benzene-exposed workers, including 83 benzene-exposed workers from a shoe factory in Wenzhou and 58 workers from a painting workshop in Wuhu, 35 workers in Wuhu were followed from 2009 to 2013, and 48 indoor workers as controls from Wenzhou. We used high-resolution melting (HRM) to quantitate human samples of DNA methylation in long interspersed nuclear element-1 (LINE-1), (6)-methylguanine-DNA methyltransferase (MGMT), and DNA mismatch repair gene human mutator L homologue 1 (hMLH1). AML-5 cells were treated with benzoquinone (BQ) and hydroquinone (HQ), and the promoter methylation of MGMT and hMLH1 was detected using the bisulfite sequencing PCR method. The degree of LINE-1 methylation in benzene-exposed workers was significantly lower than that of the controls (p<0.001), and the degree of MGMT (p<0.001) and hMLH1 (p = 0.01) methylation was significantly higher than that of the controls. The in vitro study validated the aberrant hypermethylation of hMLH1 after treatment with BQ. Among the cohort workers who were followed from 2009 to 2013, the LINE1 methylation elevated in 2013 than 2009 (p = 0.004), and premotor methylation in hMLH1 reduced in 2013 than 2009 (p = 0.045) with the reduction of the benzene exposure. This study provides evidence that benzene exposure can induce LINE-1 hypomethylation and DNA repair gene hypermethylation.
异常的 DNA 甲基化模式在癌症和暴露于环境污染物的人群中很常见。迄今为止，很少有研究检查过苯暴露工人中的异常 DNA 甲基化模式。我们招募了 141 名苯暴露工人，包括来自温州一家鞋厂的 83 名苯暴露工人和来自芜湖一家绘画车间的 58 名工人，从 2009 年到 2013 年，对 35 名芜湖工人进行了随访，48 名来自温州的室内工人作为对照组。我们使用高分辨率熔解（HRM）定量检测人类长散布核元件-1（LINE-1）、（6）-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）和 DNA 错配修复基因人类突变剂 L 同源物 1（hMLH1）的 DNA 甲基化。用苯醌（BQ）和对苯二酚（HQ）处理 AML-5 细胞，并用亚硫酸氢盐测序 PCR 法检测 MGMT 和 hMLH1 的启动子甲基化。苯暴露工人的 LINE-1 甲基化程度明显低于对照组（p<0.001），MGMT（p<0.001）和 hMLH1（p=0.01）的甲基化程度明显高于对照组。体外研究验证了 BQ 处理后 hMLH1 的异常高甲基化。在 2009 年至 2013 年随访的队列工人中，2013 年的 LINE1 甲基化水平高于 2009 年（p=0.004），2013 年的 hMLH1 前导甲基化水平低于 2009 年（p=0.045），同时苯暴露减少。这项研究提供了证据表明，苯暴露可以诱导 LINE-1 低甲基化和 DNA 修复基因高甲基化。
