Mercorio Roberta, Bonzini Matteo, Angelici Laura, Iodice Simona, Delbue Serena, Mariani Jacopo, Apostoli Pietro, Pesatori Angela Cecilia, Bollati Valentina
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122 Milan, Italy.
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122 Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Environ Res. 2017 Nov;159:452-457. doi: 10.1016/j.envres.2017.08.042. Epub 2017 Sep 18.
Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter.
Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (mean = 56.7%5mC; mean = 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: β = 5.99, p-value < 0.038; nickel: β = 17.82, p-value = 0.02; arsenic: β = 13.59, p-value < 0.015).
The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects.
吸入颗粒物已被证明会引起DNA甲基化的全身性变化。整体低甲基化与病毒序列重新激活有关，这可能与接触后发生的促炎途径激活有关。这一观察结果为研究与富含金属的颗粒物接触相关的病毒序列（包括外源性和内源性）甲基化提供了理论依据。为了验证这一假设，我们分别选择了爱泼斯坦-巴尔病毒的Wp启动子（EBV-Wp）和人类内源性逆转录病毒w的启动子（HERV-w），作为外源性和内源性逆转录病毒序列的范例，通过亚硫酸氢盐PCR焦磷酸测序进行研究。我们招募了63名在电炉钢厂工作的男性工人，他们暴露于高水平的富含金属的颗粒物中。
比较在工作周第一天（时间0-基线，休息2天后）获得的样本和工作3天后（时间1-接触后）获得的样本，EBV-Wp的平均甲基化在基线时显著高于接触后（平均值 = 56.7%5mC；平均值 = 47.9%5mC；p值 = 0.009），而HERV-w的平均甲基化没有显著差异。根据所有工作区域的测量以及研究对象在每个区域花费的时间来估计个体对可吸入颗粒物和金属的接触情况。在调整了年龄、体重指数和吸烟因素的回归模型中，PM和金属成分与EBV-Wp甲基化呈正相关（即PM10：β = 5.99，p值 < 0.038；镍：β = 17.82，p值 = 0.02；砷：β = 13.59，p值 < 0.015）。
比较基线样本和接触后样本所观察到的差异可能表明空气颗粒物会迅速诱导EBV甲基化发生变化，而EBV甲基化与PM/金属接触之间的相关性可能代表一种更稳定的适应性机制。未来研究调查更多的病毒序列组可能会更好地阐明可能的机制及其在导致全身性健康影响的促炎途径中的作用。
