受控人类暴露于柴油废气:靶支气管上皮细胞的全人类表观基因组实验。

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2021-04-09 eCollection Date: 2021-01-01 DOI:10.1093/eep/dvab003
Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind
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引用次数: 0

摘要

柴油废气(DE)是造成世界各地环境空气污染的主要因素。它是一种已知的人类致癌物,靶向呼吸系统,增加患许多疾病的风险,但关于DE暴露对人类支气管上皮细胞表观基因组的影响的研究有限。了解这种环境污染物的表观遗传学影响可以阐明与DE相关的有害健康影响的发病机制有关的生物学机制。为了估计短期DE暴露对支气管上皮表观基因组的因果影响,我们进行了一项DE暴露的对照单盲随机交叉人体实验,并分别使用支气管镜检查和Illumina 450K阵列进行数据收集和分析。在13名参与者中,11名(85%)为男性,2名(15%)为女性,12名(92%)为白人,1名(8%)为西班牙裔;平均年龄26岁 年(SD = 3.8年)。80个CpG被差异甲基化,实现了P的最小可能精确P值 = 2.44×10-4(即2/213)。在区域分析中,我们发现了两个注释在5号染色体开放阅读框63基因(C5orf63;7-CpG)和unc-45肌球蛋白伴侣A基因(UNC45A;5-CpG)上的差异甲基化区域(DMR)。DE暴露后,两种DMR均显示DNA甲基化增加。DMRs的平均因果效应范围为单个CpG的DNA甲基化增加1.5%至6.0%。总之,我们发现短期DE改变了靶支气管上皮细胞中基因的DNA甲基化,表明暴露的表观遗传学水平影响可能与肺部病理有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.

Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact P-value of P =2.44 × 10-4 (i.e. 2/213). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (C5orf63; 7-CpGs) and unc-45 myosin chaperone A gene (UNC45A; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.

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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
Correction to: To live or let die? Epigenetic adaptations to climate change-a review. Bronchial cell epigenetic aging in a human experimental study of short-term diesel and ozone exposures. Epigenetic transgenerational inheritance of toxicant exposure-specific non-coding RNA in sperm. Environmental conditions elicit a slow but enduring response of histone post-translational modifications in Mozambique tilapia. Impaired energy expenditure following exposure to either DDT or DDE in mice may be mediated by DNA methylation changes in brown adipose.
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