Nye Monica D, Fry Rebecca C, Hoyo Cathrine, Murphy Susan K
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599 ; Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC 27705.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC, 27599.
Med Epigenet. 2014;2(1):53-59. doi: 10.1159/000362336.
Increasing evidence suggest that epigenetic alterations can greatly impact human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation and disease development by controlling gene expression. In this review we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are being studied in newborns as potential biomarkers of environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms are impacted by early life exposure to iAs and Pb, and the research that is being done to move towards understanding the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early life toxic metal exposure on epigenetic changes and how these changes may result in later development of disease.
越来越多的证据表明，表观遗传改变会对人类健康产生重大影响，并且表观遗传机制（DNA甲基化、组蛋白修饰和微小RNA）在应对生命早期的环境毒物暴露方面可能尤为重要。表观基因组通过控制基因表达在胚胎发育、组织分化和疾病发展中发挥着至关重要的作用。在这篇综述中，我们讨论了目前已知的关于产前暴露于无机砷（iAs）和铅（Pb）后表观遗传改变的情况，特别关注它们对DNA甲基化的影响。然后我们描述了如何在新生儿中研究表观遗传改变作为环境毒物暴露的潜在生物标志物，以及这种方法的益处和挑战。总之，本文强调的研究表明了表观遗传机制如何受到生命早期暴露于iAs和Pb的影响，以及为理解毒物诱导的表观遗传改变与疾病发展之间的关系而正在进行的研究。尽管仍有许多未知之处，但几个研究团队正在努力了解生命早期有毒金属暴露对表观遗传变化的相关和因果影响，以及这些变化如何可能导致疾病的后期发展。
