Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001, China.
Toxicol Lett. 2016 Jan 22;243:1-6. doi: 10.1016/j.toxlet.2015.11.031. Epub 2015 Dec 3.
A matched case-control study was conducted to examine the relationship between chromium (Cr) exposure and variation in mitochondrial (mt) DNA methylation. We enrolled 29 pairs of subjects in this study; Cr exposure was confirmed in the cases by detecting blood Cr and other metal ion concentrations. DNA damage caused by Cr exposure was determined in terms of binucleated micronucleus frequency (BNMN) and mtDNA copy number. Finally, a Sequenom MassARRAY platform was applied to inspect the DNA methylation levels of mitochondrially encoded tRNA phenylalanine (MT-TF), mitochondrially encoded 12S RNA (MT-RNR1), and long interspersed nucleotide element-1 (LINE-1) genes. The blood Cr ion concentration and micronucleus frequency of the Cr-exposed group were higher than those of the control group, whereas the mtDNA copy number remained unchanged. The methylation levels of MT-TF and MT-RNR1 but not LINE-1 were significantly lower in Cr-exposed workers. Pearson correlation analysis showed that workers with higher blood Cr ion concentrations exhibited lower MT-TF and MT-RNR1 gene methylation, and multiple linear regression analysis indicated that CpG sites 1 and 2 in MT-TF and CpG site 6 in MT-RNR1 were affected. These results suggested that methylation level of mtDNA has the possibility of acting as an alternative effect biomarker for Cr exposure.
一项匹配病例对照研究旨在探讨铬（Cr）暴露与线粒体（mt）DNA 甲基化变异之间的关系。我们在这项研究中纳入了 29 对研究对象；通过检测血液 Cr 和其他金属离子浓度来确认病例组的 Cr 暴露情况。Cr 暴露导致的 DNA 损伤通过双核微核频率（BNMN）和 mtDNA 拷贝数来确定。最后，应用 Sequenom MassARRAY 平台检测线粒体编码 tRNA 苯丙氨酸（MT-TF）、线粒体编码 12S RNA（MT-RNR1）和长散布核元件-1（LINE-1）基因的 DNA 甲基化水平。Cr 暴露组的血液 Cr 离子浓度和微核频率高于对照组，而 mtDNA 拷贝数保持不变。Cr 暴露工人的 MT-TF 和 MT-RNR1 但不是 LINE-1 的甲基化水平显著降低。Pearson 相关分析显示，血液 Cr 离子浓度较高的工人表现出 MT-TF 和 MT-RNR1 基因甲基化水平降低，多元线性回归分析表明 MT-TF 的 CpG 位点 1 和 2 以及 MT-RNR1 的 CpG 位点 6 受到影响。这些结果表明，mtDNA 的甲基化水平有可能作为 Cr 暴露的替代效应生物标志物。
