Metals Exposures and DNA Methylation: Current Evidence and Future Directions

Bakulski, KM (通讯作者),Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
2022-12
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.
CURRENT ENVIRONMENTAL HEALTH REPORTS
卷号:9|期号:4|页码:673-696
收录类别:SCIE
语种
英语
来源机构
University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Southern California
资助机构
NIH(United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA)
资助信息
Support for Dr. Elkin was provided by the NIH award number T32 DK071212. Mr. Higgins was supported by the NIH award number R01 AG067592-01S1. Support for Dr. Aung was provided by the NIH award number P30 ES030284. Dr. Bakulski was supported by the NIH awards: R01 AG070897, R01 AG067592, R35 ES031686, R01 MD013299, and R01 ES025531.
被引频次(WOS)
0
被引频次(其他)
0
180天使用计数
13
2013以来使用计数
13
EISSN
2196-5412
出版年
2022-12
DOI
10.1007/s40572-022-00382-4
WOS学科分类
Public, Environmental & Occupational Health
学科领域
循证公共卫生
关键词
Metals Epigenetics DNA methylation Exposure Lead Cadmium