The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome

Abstract

BACKGROUND: It has been estimated that a substantial portion of chronic and noncommunicable diseases can be caused or exacerbated by exposure to environmental chemicals. Multiple lines of evidence indicate that early life exposure to environmental chemicals at relatively low concentrations could have lasting effects on individual and population health. Although the potential adverse effects of environmental chemicals are known to the scientific community, regulatory agencies, and the public, little is known about the mechanistic basis by which these chemicals can induce long-term or transgenerational effects. To address this question, epigenetic mechanisms have emerged as the potential link between genetic and environmental factors of health and disease. OBJECTIVES: We present an overview of epigenetic regulation and a summary of reported evidence of environmental toxicants as epigenetic disruptors. We also discuss the advantages and challenges of using epigenetic biomarkers as an indicator of toxicant exposure, using measures that can be taken to improve risk assessment, and our perspectives on the future role of epigenetics in toxicology. DISCUSSION: Until recently, efforts to apply epigenomic data in toxicology and risk assessment were restricted by an incomplete understanding of epigenomic variability across tissue types and populations. This is poised to change with the development of new tools and concerted efforts by researchers across disciplines that have led to a better understanding of epigenetic mechanisms and comprehensive maps of epigenomic variation. With the foundations now in place, we foresee that unprecedented advancements will take place in the field in the coming years.

The Molecular Mechanisms of Adaptive Response Related to Environmental Stress

“…Other data showing changes in DNA methylation patterns related to occupational exposure were reported for firefighters [ 55 ], or subjects exposed to pesticides [ 56 , 57 ], or metals [ 58 ]. A general summary with more evidence of effects of environmental chemicals on epigenetic regulation in various studies (human, animal, and in vitro) including perspectives for the future of the field of toxico-epigenomics were recently published by the epigenetic group of International Agency for Research on Cancer (IARC) [ 59 ].…”

Transgenerational Effects of Di(2-Ethylhexyl) Phthalate on Anogenital Distance, Sperm Functions and DNA Methylation in Rat Offspring

“…Epigenetic mechanisms including DNA methylation, histone modification, and expression of noncoding regulatory RNA are responsible for inherited changes in gene expression during embryogenesis and early development [ 15 ]. Among the epigenetic mechanisms involving exposure to environmental chemicals and epigenetic regulation, DNA methylation has been investigated the most extensively and is the most accurately characterized [ 16 , 17 ]. Environmental EDCs have been linked to aberrant alterations of epigenetic pathways in experimental and epidemiological studies as reviewed in [ 18 , 19 , 20 ].…”

Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

“…Epigenome-wide association studies have recently been performed on many phenotypes, traits and diseases including cancer, immune, neurodegenerative and infectious diseases, with now more than 500 EWAS published [43] and many more large-scale studies are likely to be conducted in the near future, linking complex diseases and traits with changes in the epigenome. Furthermore, DNA methylation holds the promise to explain at least a part of the influences the environment has on a phenotype [44]. Cell lines or blood cells do in most cases not appropriately recapitulate the phenotype of complex diseases, requiring the use of tissue or animal models to further our understanding of disease etiology and evaluate potential future treatments.…”