交通污染暴露對(duì)DNA甲基化及組蛋白H4K16乙酰化的影響
發(fā)布時(shí)間：2018-07-25 12:26
【摘要】：目的探討交通污染現(xiàn)場(chǎng)暴露對(duì)DNA甲基化及組蛋白H4K16乙�；挠绊�。方法30只8周齡Wistar大鼠隨機(jī)分為5組,每組6只。其中3組分別在隧道(高暴露組)、路口(中暴露組)、校園(對(duì)照組)暴露7d,另外2組分別在隧道暴露14/28d。在暴露過程中檢測(cè)3個(gè)暴露地點(diǎn)PM10和NO2的濃度。暴露實(shí)驗(yàn)分別在春季、秋季各進(jìn)行一次。暴露結(jié)束后,收集大鼠肺組織和血液樣本,焦磷酸測(cè)序法檢測(cè)基因(p53、MGMT、MAGE-A4)啟動(dòng)子區(qū)甲基化水平,酶聯(lián)免疫法檢測(cè)組蛋白H4K16乙酰化水平,并分析比較不同暴露組間DNA甲基化水平及組蛋白H4K16乙�；降牟町�。結(jié)果PM10、NO2濃度均為隧道路口校園,兩兩比較差異均有統(tǒng)計(jì)學(xué)意義;秋季PM10、NO2濃度高于春季,但差異均無統(tǒng)計(jì)學(xué)意義。秋季暴露7d后,與對(duì)照組相比,肺組織p53(P路口0.001;P隧道0.001)和MGMT(P路口0.001;P隧道=0.001)啟動(dòng)子甲基化水平顯著降低,隨著暴露時(shí)間的增加,甲基化水平進(jìn)一步降低。暴露7d后肺組織和血液MAGE-A4啟動(dòng)子甲基化水平與對(duì)照組比較,差異均無統(tǒng)計(jì)學(xué)意義;秋季隧道暴露14/28d后肺組織MAGE-A4啟動(dòng)子甲基化水平低于對(duì)照組(P14d=0.008;P28d=0.003),但仍處于高度甲基化狀態(tài)。交通污染暴露并不會(huì)導(dǎo)致組蛋白H4K16乙�；桨l(fā)生顯著改變。Spearman相關(guān)分析結(jié)果顯示,在肺組織中,PM10和p53啟動(dòng)子甲基化水平呈負(fù)相關(guān)關(guān)系(r=-0.347,P=0.038),與組蛋白H4K16乙酰化水平呈正相關(guān)(r=0.448,P=0.010);N02和p53、MGMT、MAGE-A4啟動(dòng)子甲基化水平均存在負(fù)相關(guān)(r值分別為-0.482、-0.444、-0.346,P值均0.05),與組蛋白H4K16乙�；匠收嚓P(guān)(r=0.457,P=0.009)。在血液中,MAGE-A4啟動(dòng)子甲基化水平與PM10、NO2均呈正相關(guān)(r值分別為0.395、0.431,P值均0.05)。結(jié)論 交通污染暴露可以引起p53和MGMT基因啟動(dòng)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 鹵0.431, P = 0.05). Conclusion exposure to traffic pollution can induce hypomethylation of p53 and MGMT gene promoters.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114
本文編號(hào)：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 鹵0.431, P = 0.05). Conclusion exposure to traffic pollution can induce hypomethylation of p53 and MGMT gene promoters.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114
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