Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA 02115, USA.
Part Fibre Toxicol. 2013 May 8;10:18. doi: 10.1186/1743-8977-10-18.
Mitochondria have small mitochondrial DNA (mtDNA) molecules independent from the nuclear DNA, a separate epigenetic machinery that generates mtDNA methylation, and are primary sources of oxidative-stress generation in response to exogenous environments. However, no study has yet investigated whether mitochondrial DNA methylation is sensitive to pro-oxidant environmental exposures.
We sampled 40 male participants (20 high-, 20 low-exposure) from each of three studies on airborne pollutants, including investigations of steel workers exposed to metal-rich particulate matter (measured as PM1) in Brescia, Italy (Study 1); gas-station attendants exposed to air benzene in Milan, Italy (Study 2); and truck drivers exposed to traffic-derived Elemental Carbon (EC) in Beijing, China (Study 3). We have measured DNA methylation from buffy coats of the participants. We measured methylation by bisulfite-Pyrosequencing in three mtDNA regions, i.e., the transfer RNA phenylalanine (MT-TF), 12S ribosomal RNA (MT-RNR1) gene and "D-loop" control region. All analyses were adjusted for age and smoking.
In Study 1, participants with high metal-rich PM1 exposure showed higher MT-TF and MT-RNR1 methylation than low-exposed controls (difference = 1.41, P = 0.002); MT-TF and MT-RNR1 methylation was significantly associated with PM1 exposure (beta = 1.35, P = 0.025); and MT-RNR1 methylation was positively correlated with mtDNA copy number (r = 0.36; P = 0.02). D-loop methylation was not associated with PM1 exposure. We found no effects on mtDNA methylation from air benzene (Study 2) and traffic-derived EC exposure (Study 3).
Mitochondrial MT-TF and MT-RNR1 DNA methylation was associated with metal-rich PM1 exposure and mtDNA copy number. Our results suggest that locus-specific mtDNA methylation is correlated to selected exposures and mtDNA damage. Larger studies are needed to validate our observations.
线粒体拥有独立于核 DNA 的小型线粒体 DNA（mtDNA）分子、独立的表观遗传机制，能够产生 mtDNA 甲基化，并且是对外源性环境产生氧化应激的主要来源。然而，目前还没有研究表明线粒体 DNA 甲基化是否对外源环境的促氧化剂暴露敏感。
我们从三个关于空气污染物的研究中分别对 40 名男性参与者（暴露程度高的 20 名，暴露程度低的 20 名）进行了采样，包括对意大利布雷西亚的金属富尘粒（以 PM1 衡量）暴露的钢铁工人（研究 1）、意大利米兰的空气苯暴露的加油站工作人员（研究 2）和中国北京的交通衍生元素碳（EC）暴露的卡车司机（研究 3）的调查。我们已经从参与者的血样中测量了 DNA 甲基化。我们通过亚硫酸氢盐-焦磷酸测序测量了三个 mtDNA 区域的甲基化，即转移 RNA 苯丙氨酸（MT-TF）、12S 核糖体 RNA（MT-RNR1）基因和“D 环”控制区。所有分析均根据年龄和吸烟情况进行了调整。
在研究 1 中，高金属富 PM1 暴露组的参与者 MT-TF 和 MT-RNR1 甲基化水平高于低暴露对照组（差异=1.41，P=0.002）；MT-TF 和 MT-RNR1 甲基化与 PM1 暴露显著相关（β=1.35，P=0.025）；并且 MT-RNR1 甲基化与 mtDNA 拷贝数呈正相关（r=0.36；P=0.02）。D 环甲基化与 PM1 暴露无关。我们没有发现空气苯（研究 2）和交通衍生 EC 暴露（研究 3）对 mtDNA 甲基化的影响。
线粒体 MT-TF 和 MT-RNR1 DNA 甲基化与富含金属的 PM1 暴露和 mtDNA 拷贝数相关。我们的结果表明，特定基因座的 mtDNA 甲基化与特定的暴露和 mtDNA 损伤相关。需要更大的研究来验证我们的观察结果。
