Xu Yiyi, Li Huiqi, Hedmer Maria, Hossain Mohammad Bakhtiar, Tinnerberg Håkan, Broberg Karin, Albin Maria
Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.
Unit of Metals & Health, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Environ Health. 2017 Mar 9;16(1):22. doi: 10.1186/s12940-017-0234-4.
Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure.
We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal sampling of the welders' exposure to respirable dust was performed during work hours (average sampling time: 6.8 h; range: 2.4-8.6 h) and blood pressure was measured once for each subject. We measured relative mtDNA copy number by quantitative PCR and methylation of the mitochondrial regulatory region D-loop and the tRNA encoding gene MT-TF by bisulfite-pyrosequencing. We calculated the relative number of unmethylated D-loop and MT-TF as markers of mtDNA function to explore the modification of mtDNA on the association between particle exposure and blood pressure. General linear models were used for statistical analyses.
Welders had higher mtDNA copy number (β = 0.11, p = 0.003) and lower DNA methylation of D-loop (β = -1.4, p = 0.002) and MT-TF (β = -1.5, p = 0.004) than controls. Higher mtDNA copy number was weakly associated with higher personal respirable dust exposure among welders with exposure level above 0.7 mg/m (β = 0.037, p = 0.054). MtDNA function modified the effect of welding fumes on blood pressure: welders with low mtDNA function had higher blood pressure than controls, while no such difference was found in the group with high mtDNA function.
Increased mtDNA copy number and decreased D-loop and MT-TF methylation were associated with particle-containing welding fumes exposure, indicating exposure-related oxidative stress. The modification of mtDNA function on exposure-associated increase in blood pressure may represent a mitochondria-environment interaction.
颗粒物暴露是心血管疾病的一个风险因素。线粒体DNA（mtDNA）是颗粒物暴露产生的氧化应激的主要靶点。我们旨在阐明职业性接触含颗粒物的焊接烟雾对mtDNA功能不同生物标志物的影响，进而探讨它们是否会改变颗粒物暴露与以血压衡量的心血管反应之间的关联。
我们调查了来自瑞典南部的101名焊工和127名对照者（均为不吸烟男性）。在工作时间对焊工的可吸入粉尘暴露进行个人采样（平均采样时间：6.8小时；范围：2.4 - 8.6小时），并为每个受试者测量一次血压。我们通过定量PCR测量相对mtDNA拷贝数，并通过亚硫酸氢盐焦磷酸测序测量线粒体调控区域D环和编码基因MT - TF的tRNA的甲基化。我们计算未甲基化的D环和MT - TF的相对数量作为mtDNA功能的标志物，以探讨mtDNA对颗粒物暴露与血压之间关联的修饰作用。使用一般线性模型进行统计分析。
与对照者相比，焊工的mtDNA拷贝数更高（β = 0.11，p = 0.003），D环（β = -1.4，p = 0.002）和MT - TF（β = -1.5，p = 0.004）的DNA甲基化更低。在暴露水平高于0.7 mg/m³的焊工中，较高的mtDNA拷贝数与较高的个人可吸入粉尘暴露呈弱相关（β = 0.037，p = 0.054）。mtDNA功能改变了焊接烟雾对血压的影响：mtDNA功能低的焊工血压高于对照者，而在mtDNA功能高的组中未发现这种差异。
mtDNA拷贝数增加以及D环和MT - TF甲基化降低与接触含颗粒物的焊接烟雾有关，表明存在与暴露相关氧化应激。mtDNA功能对暴露相关血压升高的修饰作用可能代表线粒体 - 环境相互作用。
