金属暴露和DNA甲基化:当前证据和未来方向。

IF 7.4 2区 医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Current Environmental Health Reports Pub Date : 2022-12-01 Epub Date: 2022-10-25 DOI:10.1007/s40572-022-00382-4
Elana R Elkin, Cesar Higgins, Max T Aung, Kelly M Bakulski
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引用次数: 6

摘要

审查目的:接触必需和非必需金属的情况普遍存在。金属暴露与表观遗传学,特别是DNA甲基化的差异有关。关于金属暴露类型、时间和水平,以及DNA甲基化关联程度和再现性的证据强度尚不清楚。关注最近3年,我们回顾了人类流行病学证据(n = 26项研究)和毒理学动物模型证据(n = 18项研究),以了解金属暴露与DNA甲基化之间的关联。最近的发现:在人类中,最多的研究集中在铅暴露,其次是镉和砷的研究。大约一半的研究考虑了宫内期间的金属暴露,并用全基因组Illumina阵列测量了新生儿血液或胎盘中的DNA甲基化。很少有研究进行正式的复制测试或荟萃分析。金属和表观遗传学的毒理学研究在模型系统中具有多样性(以小鼠、大鼠、果蝇、罗非鱼和斑马鱼为代表),用于DNA甲基化测量的组织(肝脏、睾丸、卵巢、心脏、血液、大脑、肌肉、肺、肾、整个胚胎)具有高度异质性,用于DNA甲酯化评估的技术多种多样(全局、基因特异性、全基因组)。毒理学研究中测试的最常见的金属是铅和镉。总之,最近综述的研究为产前金属暴露的DNA甲基化特征提供了最有力的证据。还有越来越多的流行病学证据支持成年人接触铅、砷和镉的DNA甲基化特征。通过纳入流行病学和毒理学方法,金属和DNA甲基化领域得到了加强,通过协调工作或整合研究分析可以取得进一步进展。在理解对金属暴露的序列特异性表观遗传反应的分子基础、在全基因组分析框架中处理暴露混合物的方法以及促进合作测试的管道方面,未来的进展将继续推动该领域的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metals Exposures and DNA Methylation: Current Evidence and Future Directions.

Purpose of the review: Exposure to essential and non-essential metals is widespread. Metals exposure is linked to epigenetic, particularly DNA methylation, differences. The strength of evidence with respect to the metal exposure type, timing, and level, as well as the DNA methylation association magnitude, and reproducibility are not clear. Focusing on the most recent 3 years, we reviewed the human epidemiologic evidence (n = 26 studies) and the toxicologic animal model evidence (n = 18 studies) for associations between metals exposure and DNA methylation.

Recent findings: In humans, the greatest number of studies focused on lead exposure, followed by studies examining cadmium and arsenic. Approximately half of studies considered metals exposure during the in utero period and measured DNA methylation with the genome-wide Illumina arrays in newborn blood or placenta. Few studies performed formal replication testing or meta-analyses. Toxicology studies of metals and epigenetics had diversity in model systems (mice, rats, drosophila, tilapia, and zebrafish were represented), high heterogeneity of tissues used for DNA methylation measure (liver, testis, ovary, heart, blood, brain, muscle, lung, kidney, whole embryo), and a variety of technologies used for DNA methylation assessment (global, gene specific, genome-wide). The most common metals tested in toxicologic studies were lead and cadmium. Together, the recent studies reviewed provide the strongest evidence for DNA methylation signatures with prenatal metals exposures. There is also mounting epidemiologic evidence supporting lead, arsenic, and cadmium exposures with DNA methylation signatures in adults. The field of metals and DNA methylation is strengthened by the inclusion of both epidemiology and toxicology approaches, and further advancements can be made by coordinating efforts or integrating analyses across studies. Future advances in understanding the molecular basis of sequence specific epigenetic responses to metals exposures, methods for handling exposure mixtures in a genome-wide analytic framework, and pipelines to facilitate collaborative testing will continue to advance the field.

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来源期刊
CiteScore
13.60
自引率
1.30%
发文量
47
期刊介绍: Current Environmental Health Reports provides up-to-date expert reviews in environmental health. The goal is to evaluate and synthesize original research in all disciplines relevant for environmental health sciences, including basic research, clinical research, epidemiology, and environmental policy.
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