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环境空气中不同浓度颗粒物暴露对小鼠肺部 DNA 和 RNA 甲基化及其逆转的影响。

The global DNA and RNA methylation and their reversal in lung under different concentration exposure of ambient air particulate matter in mice.

机构信息

Laboratory of Environmental Criteria and Risk Assessment & Environmental Standards Institute, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

Senior High School, Beijing No.171 High School, 100013, China.

出版信息

Ecotoxicol Environ Saf. 2019 May 15;172:396-402. doi: 10.1016/j.ecoenv.2019.01.111. Epub 2019 Feb 4.

DOI:10.1016/j.ecoenv.2019.01.111
PMID:30731271
Abstract

Particulate matter (PM) in air pollution is a pervasive risk factor in pulmonary diseases that are always associated with gene expression level alterations in many specific-genes. DNA methylation (5-methylcytosine [5mC]) and RNA methylation (N6-methyladenine [6 mA]) influence the gene expression from transcription and post-transcription level, and the DNA hydroxymethylation (5-hydroxymethylcytosine [5hmC]) is the oxidized form of 5mC. In the present study, the levels of global 5mC, 5hmC and 6 mA of lungs in experimental mice were investigated. We divided the animals into 3 groups randomly, the group 1 was exposed to heavy PM for 24 h in the unfiltered chamber, the group 2 was exposed to filtered air in the filtered chamber, and the group 3 was 10 of the mice in the group 1 after 24 h exposure and then being moved to the filtered chamber for further 120 h exposure. The morphology of lungs showed that acute PM exposure impaired the structure of pulmonary alveolus. Meanwhile, the global level of DNA methylation was decreased, and DNA hydroxymethylation and RNA methylation levels were increased in lungs after PM exposure for only 24 h. Very notably, after being exposed in purified air for 120 h, the pulmonary morphology, the global levels of DNA methylation, DNA hydroxymethylation and RNA methylation of lungs were all reversed. The present study clearly demonstrated the alteration of DNA and RNA methylation after acute heavy PM exposure and emphasized the reversal of the symptoms caused by PM exposure after the air purification, which provided us a new idea for the intervention of the adverse health effects from air pollution. CAPSULE: Acute PM exposure resulted in reduced global DNA methylation and increased global DNA hydroxymethylcytosine and RNA methylation, and air purification reversed these alterations.

摘要

大气污染中的颗粒物(PM)是肺部疾病的普遍风险因素,总是与许多特定基因的基因表达水平改变有关。DNA 甲基化(5-甲基胞嘧啶[5mC])和 RNA 甲基化(N6-甲基腺嘌呤[6m A])影响转录和转录后水平的基因表达,而 DNA 羟甲基化(5-羟甲基胞嘧啶[5hmC])是 5mC 的氧化形式。在本研究中,研究了实验小鼠肺部的全局 5mC、5hmC 和 6m A 水平。我们将动物随机分为 3 组,第 1 组在未过滤室中暴露于重 PM 24 h,第 2 组在过滤室中暴露于过滤空气,第 3 组为第 1 组中的 10 只小鼠,暴露 24 h 后转移到过滤室中进一步暴露 120 h。肺部形态学显示急性 PM 暴露损害了肺泡结构。同时,PM 暴露仅 24 h 后,肺部的 DNA 甲基化整体水平降低,DNA 羟甲基化和 RNA 甲基化水平升高。非常值得注意的是,在纯化空气暴露 120 h 后,肺部形态、DNA 甲基化、DNA 羟甲基化和 RNA 甲基化的整体水平均得到逆转。本研究清楚地表明急性重度 PM 暴露后 DNA 和 RNA 甲基化的改变,并强调了空气净化后 PM 暴露引起的症状的逆转,这为我们干预空气污染对健康的不良影响提供了新的思路。

摘要

急性 PM 暴露导致全局 DNA 甲基化减少,全局 DNA 羟甲基化和 RNA 甲基化增加,空气净化可逆转这些改变。

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