Humans are easily exposed to environmentally hazardous factors in industrial sites or daily life. In addition, exposure to various substances and not just one harmful substance is common. However, research on the effects of combined exposure on humans is limited. Therefore, this study examined the effects of combined exposure to volatile organic compounds (VOCs) on the human body. We separated 193 participants into four groups according to their work-related exposure (nonexposure, toluene exposure, toluene and xylene exposure, and toluene, ethylbenzene, and xylene exposure). We then identified the methylation level and long noncoding RNA (lncRNA) levels by omics analyses, and performed an integrated analysis to examine the change of gene expression. Thereafter, the effects of combined exposure to environmental hazards on the human body were investigated and analyzed. Exposure to VOCs was found to negatively affect the development and maintenance of the nervous system. In particular, the MALAT1 lncRNA was found to be significantly reduced in the complex exposure group, and eight genes were significantly downregulated by DNA hypermethylation. The downregulation of these genes could cause a possible decrease in the density of synapses as well as the number and density of dendrites and spines. In summary, we found that increased combined exposure to environmental hazards could lead to additional epigenetic changes, and consequently abnormal dendrites, spines, and synapses, which could damage motor learning or spatial memory. Thus, lncRNA MALAT1 or FMR1 could be novel biomarkers of neurotoxicity to identify the negative health effects of VOC complex exposure.

中文翻译：

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联合暴露于环境危害引起的表观遗传变化的多组学数据综合分析

人类在工业现场或日常生活中很容易暴露于环境有害因素中。此外，接触各种物质而不仅仅是一种有害物质是常见的。然而，关于联合暴露对人类影响的研究是有限的。因此，本研究考察了联合暴露于挥发性有机化合物 (VOC) 对人体的影响。我们根据与工作相关的暴露（未暴露、甲苯暴露、甲苯和二甲苯暴露以及甲苯、乙苯和二甲苯暴露）将 193 名参与者分为四组。然后我们通过组学分析确定了甲基化水平和长链非编码 RNA (lncRNA) 水平，并进行了综合分析以检查基因表达的变化。此后，调查和分析了联合暴露于环境危害对人体的影响。研究发现，接触 VOC 会对神经系统的发育和维持产生负面影响。特别是，发现复杂暴露组中 MALAT1 lncRNA 显着减少，有 8 个基因被 DNA 高甲基化显着下调。这些基因的下调可能导致突触密度以及树突和刺的数量和密度降低。总之，我们发现增加对环境危害的综合暴露可能导致额外的表观遗传变化，从而导致异常的树突、棘突和突触，这可能会损害运动学习或空间记忆。因此，