Mailman School of Public Health, Columbia University, New York, NY 10032;
Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3503-3508. doi: 10.1073/pnas.1618545114. Epub 2017 Mar 13.
Acute exposure to fine particle (PM) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM (250 μg/m) under placebo, and PM (250 μg/m) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B, and 1 mg/d vitamin B), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4 T-helper cells. PM induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM effect by 102% ( = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM effects, with possible significant public health benefit in areas with frequent PM peaks.
急性暴露于细颗粒物(PM)会引起 DNA 甲基化变化,这些变化与炎症和氧化应激有关。我们进行了一项交叉试验,以确定 B 族维生素补充是否可以避免这种变化。10 名健康成年人在安慰剂、PM(250μg/m)下的安慰剂和 PM(250μg/m)下的 B 族维生素补充剂(2.5mg/d 叶酸、50mg/d 维生素 B 和 1mg/d 维生素 B)下分别接受了 2 小时的对照暴露实验。我们使用 Infinium HumanMethylation450 BeadChip 在外周 CD4 辅助性 T 细胞中对每个实验前后的全基因组甲基化进行了分析。PM 诱导了与线粒体氧化能量代谢相关的基因的甲基化变化。B 族维生素补充剂可以预防这些变化。同样,PM 使线粒体 DNA 含量减少了 11.1%(95%置信区间为 0.4%至 21.7%;=0.04),与假暴露相比,B 族维生素补充剂使 PM 的影响减少了 102%(=0.01)。我们的研究表明,个体水平的预防可能被用来补充法规,并控制潜在的与不良 PM 影响相关的机制途径,在经常出现 PM 峰值的地区可能会带来显著的公共卫生益处。