Alvarado-Cruz Isabel, Sánchez-Guerra Marco, Hernández-Cadena Leticia, De Vizcaya-Ruiz Andrea, Mugica Violeta, Pelallo-Martínez Nadia Azenet, Solís-Heredia María de Jesús, Byun Hyang-Min, Baccarelli Andrea, Quintanilla-Vega Betzabet
Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico.
National Institute of Public Health, Mexico City, Mexico.
Mutat Res Genet Toxicol Environ Mutagen. 2017 Jan;813:27-36. doi: 10.1016/j.mrgentox.2016.11.007. Epub 2016 Nov 22.
DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards. Methylation (5mC) of long interspersed nuclear element-1 (LINE1) and DNA repair gene (OGG1, APEX, and PARP1) was assessed by pyrosequencing in peripheral mononuclear cells, DNA damage by comet assay and DNA oxidation by 8-OHdG content. PAH and metal contents in PM (≤10μm aerodynamic diameter) were determined by HPLC-MS and ICP-AES, respectively. Multiple regression analysis between DNA methylation, DNA damage, and PM exposure showed that PM was significantly associated with oxidative DNA damage; a 1% increase in 5mC at all CpG sites in PARP1 promoter was associated with a 35% increase in 8-OHdG, while a 1% increase at 1, 2, and 3 CpG sites resulted in 38, 9, and 56% increments, respectively. An increase of 10pg/m in benzo[b]fluoranthene content of PM was associated with a 6% increase in LINE1 methylation. Acenaphthene, indene [1,2,3-cd] pyrene, and pyrene concentrations correlated with higher dinucleotide methylation in OGG1, APEX and PARP1 genes, respectively. Vanadium concentration correlated with increased methylation at selected APEX and PARP1 CpG sites. DNA repair gene methylation was significantly correlated with DNA damage and with specific PM-associated PAHs and Vanadium. Data suggest that exposure to PM and its components are associated with differences in DNA methylation of repair genes in children, which may contribute to DNA damage.
DNA修复基因中的DNA甲基化参与DNA损伤调控。吸附有金属和多环芳烃（PAHs）等物质的颗粒物（PM）与不良健康后果有关，并且可能会改变DNA甲基化。为了评估PM暴露对重复元件、基因特异性DNA甲基化和DNA损伤的影响，我们对来自墨西哥城大都市区（MAMC）一个城市化工业区的150名学童（7 - 10岁）进行了一项横断面研究，该地区的PM浓度经常高于安全标准。通过焦磷酸测序在外周血单核细胞中评估长散在核元件1（LINE1）和DNA修复基因（OGG1、APEX和PARP1）的甲基化（5mC），通过彗星试验评估DNA损伤，通过8 - OHdG含量评估DNA氧化。分别通过HPLC - MS和ICP - AES测定PM（空气动力学直径≤10μm）中的PAH和金属含量。DNA甲基化、DNA损伤和PM暴露之间的多元回归分析表明，PM与氧化性DNA损伤显著相关；PARP1启动子所有CpG位点的5mC增加1%与8 - OHdG增加35%相关，而在第1、2和3个CpG位点增加1%分别导致增加38%、9%和56%。PM中苯并[b]荧蒽含量每增加10pg/m与LINE1甲基化增加6%相关。苊、茚并[1,2,3 - cd]芘和芘的浓度分别与OGG1、APEX和PARP1基因中更高的二核苷酸甲基化相关。钒浓度与选定的APEX和PARP1 CpG位点甲基化增加相关。DNA修复基因甲基化与DNA损伤以及特定的与PM相关的PAHs和钒显著相关。数据表明，儿童暴露于PM及其成分与修复基因DNA甲基化的差异有关，这可能导致DNA损伤。
