癌变·畸变·突变2025，Vol.37Issue(3)：183-189,7.DOI:10.3969/j.issn.1004-616x.2025.03.002
PM2.5短期暴露人群外周血淋巴细胞MGMT甲基化修饰改变及其生物学意义
Altered MGMTmethylation and biological significance in blood lymphocytes from short-term PM2.5-exposed population
摘要
Abstract
OBJECTIVE:This study aimed to screen for methylation changes at MGMT CpG sites and their biological significance in blood lymphocytes from healthy adults who were exposed to short-term PM2.5.METHODS:Thirty healthy male undergraduates from Hebei Medical University participated in a 35-day panel study,during which daily PM2.5 exposure was assessed based on individual time-activity patterns.MGMT methylation was quantified by pyrophosphate sequencing of DNA extracted from peripheral blood lymphocytes at low and high PM2.5 exposure time points.Additionally,urinary 1-hydroxypyrene(1-OHP),8-hydroxy-2′-deoxyguanosine(8-OHdG),and plasma tumor necrosis factor-alpha(TNF-α)levels were analyzed.RESULTS:The average ambient PM2.5 concentration for the three days before the high exposure(110.09 μg/m3)was 2.32 times higher than at low exposure(47.37 μg/m3),while urinary 1-OHP levels,indicating internal exposure,were 1.73 times higher(P<0.01).Urinary 8-OHdG and plasma TNF-α levels were 1.18-fold and 1.66-fold higher,respectively,than those under low exposure(all P<0.01).Increase in oxidative DNA damage and inflammatory response was accompanied by a decrease in the methylation levels of MGMT CpG sites 1,3,4,5,6,and 10 by 37.31%,42.60%,19.69%,15.29%,34.95%and 32.12%,respectively(all P<0.05).Hypomethylation at CpG sites 1,3,and 10 was negatively correlated with urinary 1-OHP(β≥-0.40,all P<0.05),8-OHdG(β≥-0.46,all P<0.05),and TNF-α(β≥-0.26,all P<0.05).Altered methylation at these hot CpG sites was negatively correlated with the moving average concentrations of PM2.5(lag0-2)(β≥-0.53,all P<0.05).CONCLUSION:MGMT hypomethylation modifications at hot CpG sites 1,3 and 10 were found to be associated with both external and internal PM2.5 exposure as well as biological effects,indicating their potential as biomarkers for PM2.5 exposure in the population.关键词
短期PM2.5暴露/定组研究/MGMT基因/DNA甲基化/特异性CpG位点Key words
short-term PM2.5 exposure/panel study/MGMT gene/DNA methylation/specific CpG sites分类
预防医学引用本文复制引用
刘文洁,叶丽珠,蒋悦,陈燊,陈雯..PM2.5短期暴露人群外周血淋巴细胞MGMT甲基化修饰改变及其生物学意义[J].癌变·畸变·突变,2025,37(3):183-189,7.基金项目
国家重点研发计划(2023YFC3708304) （2023YFC3708304）
