This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4 (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI)] were studied using bisulfite pyrosequencing. Analysis of global DNA methylation levels and hydroxymethylation did not reveal significant difference between the MWCNT-exposed and control groups. No significant changes in Cytosine-phosphate-Guanine (CpG) site methylation were observed for the LINE1 (L1RE1) elements. Further analysis of gene-specific DNA methylation showed a significant change in methylation for DNMT1, ATM, SKI, and HDAC4 promoter CpGs in MWCNT-exposed workers. Since DNA methylation plays an important role in silencing/regulation of the genes, and many of these genes have been associated with occupational and smoking-induced diseases and cancer (risk), aberrant methylation of these genes might have a potential effect in MWCNT-exposed workers.

中文翻译：

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多壁碳纳米管在工作场所暴露引起的DNA甲基化变化

这项研究旨在评估由于职业性暴露于多壁碳纳米管（MWCNT）而引起的血细胞表观遗传学改变。研究人群包括来自同一工作场所的MWCNT暴露工人（n = 24）和未暴露的对照组（n = 43）。我们使用验证的液相色谱串联质谱（LC-MS / MS）方法测量了第5个胞嘧啶残基上的总体DNA甲基化/羟甲基化水平。LINE1可逆转座子元件1（L1RE1）元件的序列特异性甲基化，以及与表观遗传调控相关的功能重要基因的启动子区域[DNA甲基转移酶-1（DNMT1）和组蛋白脱乙酰基酶4（HDAC4））]，DNA损伤/修复和细胞周期途径[核蛋白，组蛋白转录的共激活因子/ ATM丝氨酸/苏氨酸激酶（NPAT / ATM） ]和潜在的转化生长因子β（TGF-β）阻遏物[SKI原癌基因（SKI）]使用亚硫酸氢盐焦磷酸测序进行了研究。总体DNA甲基化水平和羟甲基化的分析未发现暴露于MWCNT的组与对照组之间存在显着差异。对于LINE1（L1RE1）元素，未观察到胞嘧啶-磷酸-鸟嘌呤（CpG）位点甲基化的显着变化。基因特异性DNA甲基化的进一步分析显示DNMT1，ATM，SKI和HDAC4的甲基化发生了重大变化MWCNT暴露工人中的启动子CpGs。由于DNA甲基化在基因的沉默/调控中起着重要作用，并且其中许多基因与职业和吸烟引起的疾病和癌症（风险）有关，因此这些基因的异常甲基化可能在暴露于MWCNT的情况下具有潜在的作用。工人。