交通污染暴露对DNA甲基化的影响

发布时间：2018-06-13 02:45

本文选题：交通污染 + DNA甲基化　；参考：《环境科学》2017年08期

【摘要】：探讨交通污染现场暴露对DNA甲基化的影响.30只8周龄Wistar大鼠按随机数字表法随机分5组,每组6只.其中3组分别在隧道(高暴露组)、路口(中暴露组)、校园(对照组)暴露7 d,另外2组分别在隧道暴露14 d/28 d.在暴露过程中检测3个暴露地点PM_(10)、NO_2的浓度.暴露实验分别在春季、秋季各进行一次.暴露结束后,焦磷酸测序法检测肺组织和血液中DNA(p53、MGMT、MAGE-A4)甲基化水平,并分析比较不同暴露组间DNA甲基化水平的差异.结果表明,PM_(10)、NO_2浓度均为隧道(高暴露组)路口(中暴露组)校园(对照组),差异具有统计学意义.秋季暴露7 d后,与对照组相比,肺组织中p53(P_(路口)=0.016;P_(隧道)=0.019)、MGMT(P_(路口)=0.002;P_(隧道)=0.003)启动子甲基化水平显著降低,随着暴露时间的增加,甲基化水平进一步降低;MAGE-A4启动子区处于高度甲基化状态,在肺组织和血液中,均未发现MAGE-A4启动子甲基化水平在三暴露组间存在显著的统计学差异.7d暴露对肺组织中DNA甲基化水平的影响更大,但随着暴露时间的增加,肺组织和血液中DNA甲基化水平改变模式趋于一致.Spearman相关分析结果显示,在肺组织中,PM_(10)和p53甲基化水平呈负相关关系(r=-0.347;P=0.038);NO_2和p53、MGMT、MAGE-A4甲基化水平均存在负相关(r值分别为-0.482、-0.444、-0.346,P值均0.05).在血液中,MAGE-A4甲基化水平与PM_(10)、NO_2均呈正相关(r值分别为0.395、0.431,P值均0.05).交通污染暴露会引起p53、MGMT启动子低甲基化.
[Abstract]:The effects of traffic pollution exposure on DNA methylation in.30 only 8 weeks old Wistar rats were randomly divided into 5 groups according to random number table method, 6 in each group. Among them, 3 groups were in tunnel (high exposure group), intersection (middle exposure group), campus (control group) exposed 7 d, the other 2 groups were exposed to 14 d/28 D. during the exposure process to detect PM_ (1) during the exposure process. 0) the concentration of NO_2. The exposure test was carried out in the spring and autumn. After the exposure, the methylation level of DNA (p53, MGMT, MAGE-A4) in lung tissue and blood was detected by pyrosequencing, and the difference of DNA methylation level between different exposure groups was compared. The results showed that PM_ (10), NO_2 concentration was the intersection (high exposure group) intersection (medium exposure). On campus (control group), the difference was statistically significant. After 7 d exposure in the autumn, compared with the control group, p53 (P_ (intersection) =0.016; P_ (tunnel) =0.019) in the lung tissue, MGMT (P_ (intersection) =0.002; P_ (tunnel) =0.003), the methylation level of the promoter decreased significantly, and the methylation level was further reduced with the increase of exposure time; the MAGE-A4 promoter region was in a further decrease. High methylation status, no significant difference in the level of MAGE-A4 promoter methylation between the three exposure groups was not found in the lung tissue and blood. The effect of.7d exposure on the level of DNA methylation in lung tissues was greater, but the pattern of DNA methylation in the lung tissue and blood tended to be consistent with.Spearman as the exposure time increased. The correlation analysis showed that in lung tissue, PM_ (10) and p53 methylation levels were negatively correlated (r=-0.347; P=0.038), and NO_2 and p53, MGMT, MAGE-A4 methylation levels were negatively correlated (R values were -0.482, -0.444, -0.346, and 0.05). 1, P = 0.05). Traffic pollution exposure can cause p53 and MGMT promoter hypomethylation.
【作者单位】：浙江大学公共卫生学院环境表观遗传实验室;浙江大学医学院附属邵逸夫医院;浙江大学公共卫生学院毒理学研究室;浙江大学公共卫生实验教学中心;浙江大学药学院生化药学研究室;
【基金】：国家自然科学基金项目(81372953,81673124)
【分类号】：X51;X734.2

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