| 交通污染暴露对DNA甲基化的影响 |
| 摘要点击 1364 全文点击 644 投稿时间：2017-01-11 修订日期：2017-03-07 |
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| 中文关键词 交通污染 DNA甲基化 p 53 MGMT 暴露 |
| 英文关键词 traffic-related air pollution DNA methylation p 53 MGMT exposure |
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| 中文摘要 |
| 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PM10、NO2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（p 53、MGMT、MAGE-A 4）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，PM10、NO2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p 53 （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-A 4 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-A 4 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，PM10和p 53 甲基化水平呈负相关关系（r=-0.347；P=0.038）；NO2和p 53 、MGMT、MAGE-A 4 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-A 4 甲基化水平与PM10、NO2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. |
| 英文摘要 |
| The goal of the present study was to explore the effects of traffic-related air pollution exposure on DNA methylation. Into five groups of 6, 30 healthy Wistar rats were randomly divided. Three groups of rats were then exposed to traffic-related air pollution at high (tunnel), moderate (crossroad), and low (control) pollution levels for 7 d, whereas the two other groups were exposed in the tunnel for 14 d/28 d. The levels of PM10 and NO2 were measured during the exposure. The study was performed in spring and autumn, and lung tissue and blood were collected after the exposure. Promoter methylation levels of p 53 , MGMT, and MAGE-A 4 were quantified via pyrosequencing. The levels of PM10 and NO2 in the crossroad and tunnel groups were significantly higher than those in the control group. After 7 d exposure in autumn, promoter methylation levels of p 53 and MGMT in lung tissue significantly decreased, and the methylation status continued to decrease with increasing exposure time; MAGE-A 4 was highly methylated and showed no difference among the three groups. DNA methylation in lung tissue was more likely to be changed compared with that in blood during 7 d exposure. As the exposure time increased, DNA methylation changes between blood and lung tissue started to coincide. In lung tissue, PM10 exposure was significantly associated with decreased p 53 promoter methylation (r=-0.347, P=0.038) and NO2 exposure was significantly associated with decreased promoter methylation of p 53, MGMT, and MAGE-A 4 (r=-0.482, -0.444, and -0.346, respectively; P< 0.05). In blood, PM10 and NO2 were significantly and positively associated with MAGE-A 4 promoter methylation (r=0.395 and 0.431, respectively; P< 0.05). Traffic-related air pollution exposure may induce promoter hypomethylation of p 53 and MGMT. |
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