交通污染暴露对DNA甲基化及组蛋白H4K16乙酰化的影响
发布时间：2018-07-25 12:26
【摘要】：目的探讨交通污染现场暴露对DNA甲基化及组蛋白H4K16乙酰化的影响。方法30只8周龄Wistar大鼠随机分为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7d,另外2组分别在隧道暴露14/28d。在暴露过程中检测3个暴露地点PM10和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,收集大鼠肺组织和血液样本,焦磷酸测序法检测基因(p53、MGMT、MAGE-A4)启动子区甲基化水平,酶联免疫法检测组蛋白H4K16乙酰化水平,并分析比较不同暴露组间DNA甲基化水平及组蛋白H4K16乙酰化水平的差异。结果PM10、NO2浓度均为隧道路口校园,两两比较差异均有统计学意义;秋季PM10、NO2浓度高于春季,但差异均无统计学意义。秋季暴露7d后,与对照组相比,肺组织p53(P路口0.001;P隧道0.001)和MGMT(P路口0.001;P隧道=0.001)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。暴露7d后肺组织和血液MAGE-A4启动子甲基化水平与对照组比较,差异均无统计学意义;秋季隧道暴露14/28d后肺组织MAGE-A4启动子甲基化水平低于对照组(P14d=0.008;P28d=0.003),但仍处于高度甲基化状态。交通污染暴露并不会导致组蛋白H4K16乙酰化水平发生显著改变。Spearman相关分析结果显示,在肺组织中,PM10和p53启动子甲基化水平呈负相关关系(r=-0.347,P=0.038),与组蛋白H4K16乙酰化水平呈正相关(r=0.448,P=0.010);N02和p53、MGMT、MAGE-A4启动子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),与组蛋白H4K16乙酰化水平呈正相关(r=0.457,P=0.009)。在血液中,MAGE-A4启动子甲基化水平与PM10、NO2均呈正相关(r值分别为0.395、0.431,P值均0.05)。结论 交通污染暴露可以引起p53和MGMT基因启动子低甲基化。
[Abstract]:Objective to investigate the effects of traffic pollution site exposure on DNA methylation and histone H4K16 acetylation. Methods 30 8-week-old Wistar rats were randomly divided into 5 groups with 6 rats in each group. The three groups were exposed to the tunnel (high exposure group), the intersection (middle exposure group), the campus (control group) for 7 days, the other two groups were exposed to 14 / 28 days in the tunnel. The concentrations of PM10 and NO2 in three exposure sites were detected during exposure. Exposure experiments were conducted in spring and autumn respectively. After exposure, lung tissue and blood samples of rats were collected, methylation level of promoter region of gene (p53) MGMT-MAGE-A4 was detected by pyrosequencing and acetylation of histone H4K16 was detected by enzyme-linked immunosorbent assay (Elisa). The levels of DNA methylation and histone H4K16 acetylation were analyzed and compared among different exposure groups. Results the concentrations of PM10O _ 2 in tunnel junctions were significantly higher in autumn than in spring, but the differences were not statistically significant. After 7 days of exposure in autumn, the promoter methylation level of p53 (0.001 P tunnel 0.001 at P junction) and 0.001 P tunnel 0.001 at MGMT (P junction was significantly lower than that of control group, and the methylation level further decreased with the increase of exposure time. There was no significant difference between lung tissue and blood MAGE-A4 promoter methylation level compared with control group after 7 d exposure, but the level of MAGE-A4 promoter methylation in lung tissue was lower than that in control group (P14 d + 0.008 + P28 d + 0.003) after 14 / 28 d of tunnel exposure in autumn, but it was still in high methylation state. There was no significant change in acetylation level of histone H4K16 after exposure to traffic pollution. Spearman correlation analysis showed that, There was a negative correlation between methylation level of PM10 and p53 promoter in lung tissue (r = -0.347P0. 038), and a positive correlation with histone H4K16 acetylation level (r = 0. 448%) and methylation level of p53 MGMTT MAGE-A4 promoter (P < 0. 05) and histone H4K16 acetyl level (P = 0. 05). A positive correlation was found between the two groups (r = 0. 457, P < 0. 009). The methylation level of MAGE-A4 promoter was positively correlated with PM10NO2 in blood (r = 0.395 卤0.431, P = 0.05). Conclusion exposure to traffic pollution can induce hypomethylation of p53 and MGMT gene promoters.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114
本文编号：2143813
[Abstract]:Objective to investigate the effects of traffic pollution site exposure on DNA methylation and histone H4K16 acetylation. Methods 30 8-week-old Wistar rats were randomly divided into 5 groups with 6 rats in each group. The three groups were exposed to the tunnel (high exposure group), the intersection (middle exposure group), the campus (control group) for 7 days, the other two groups were exposed to 14 / 28 days in the tunnel. The concentrations of PM10 and NO2 in three exposure sites were detected during exposure. Exposure experiments were conducted in spring and autumn respectively. After exposure, lung tissue and blood samples of rats were collected, methylation level of promoter region of gene (p53) MGMT-MAGE-A4 was detected by pyrosequencing and acetylation of histone H4K16 was detected by enzyme-linked immunosorbent assay (Elisa). The levels of DNA methylation and histone H4K16 acetylation were analyzed and compared among different exposure groups. Results the concentrations of PM10O _ 2 in tunnel junctions were significantly higher in autumn than in spring, but the differences were not statistically significant. After 7 days of exposure in autumn, the promoter methylation level of p53 (0.001 P tunnel 0.001 at P junction) and 0.001 P tunnel 0.001 at MGMT (P junction was significantly lower than that of control group, and the methylation level further decreased with the increase of exposure time. There was no significant difference between lung tissue and blood MAGE-A4 promoter methylation level compared with control group after 7 d exposure, but the level of MAGE-A4 promoter methylation in lung tissue was lower than that in control group (P14 d + 0.008 + P28 d + 0.003) after 14 / 28 d of tunnel exposure in autumn, but it was still in high methylation state. There was no significant change in acetylation level of histone H4K16 after exposure to traffic pollution. Spearman correlation analysis showed that, There was a negative correlation between methylation level of PM10 and p53 promoter in lung tissue (r = -0.347P0. 038), and a positive correlation with histone H4K16 acetylation level (r = 0. 448%) and methylation level of p53 MGMTT MAGE-A4 promoter (P < 0. 05) and histone H4K16 acetyl level (P = 0. 05). A positive correlation was found between the two groups (r = 0. 457, P < 0. 009). The methylation level of MAGE-A4 promoter was positively correlated with PM10NO2 in blood (r = 0.395 卤0.431, P = 0.05). Conclusion exposure to traffic pollution can induce hypomethylation of p53 and MGMT gene promoters.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114
【参考文献】
相关期刊论文 前7条
1 蒋伟超;吴思英;柯跃斌;;环境化学物暴露与儿童急性淋巴细胞白血病风险的关联研究[J];中华预防医学杂志;2016年10期
2 张云权;马露;朱耀辉;龙璇;李锐;王素青;;季节和温度在颗粒物暴露对死亡率影响中的修饰效应[J];中华预防医学杂志;2015年01期
3 刘昕能;金永堂;徐沛维;陈春梅;谭聪;;Line-1甲基化与非小细胞肺癌临床特征的关系[J];中华医学遗传学杂志;2014年03期
4 徐莹莹;桑梅香;单保恩;;肿瘤抗原MAGE与p53关系的研究进展[J];癌变·畸变·突变;2013年02期
5 孟夏;陈仁杰;阚海东;;我国交通来源大气污染现状及其健康危害[J];中华预防医学杂志;2011年11期
6 谭聪;金永堂;;常见空气污染的表观遗传效应研究进展[J];浙江大学学报(医学版);2011年04期
7 张秋丽;林蓉;于莹莹;宋宏;杨轶戬;蔡琳;钟洁莹;杨翠辉;;城市公交车司机交通污染暴露水平评估[J];中国卫生检验杂志;2009年07期
，本文编号：2143813
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