Effects of Environmentally Acquired Heavy Metals and Nutrients on the Epigenome and Phenotype

Abstract

Cadmium, arsenic, mercury and lead are ubiquitous environmental contaminants that tend to co-occur. Unlike organic compounds that are chemically, biologically, or photo-degraded, these metals persist in the environment for indefinite periods. Although protein disruption/misfolding, generation of oxidative stress, and endocrine disruption are known effects of toxic metal exposure, beyond the known toxic effects of high dose exposure, mechanisms causing these effects, especially at low chronic doses, are still largely unknown. Epigenetics is emerging as a viable mechanistic framework to explain how the environment interacts with the genome to alter disease risk. Alterations in DNA methylation, histone marks and chromatin structure have been proposed as useful exposure assessment biomarkers that can substantially improve assessment of risk in etiologic studies where exposure occurs early during the life course. If developed into exposure-specific biomarkers, these epigenetic marks can be a powerful tool to identify populations exposed to low doses where phenotypic response may not be immediately apparent, and also to evaluate the efficacy of therapeutic and public health interventions. This could be particularly important as exposed populations tend to be the socioeconomically disadvantaged who have limited contact with the health care system. In this review, we provide an overview of the current state of literature on heavy-metal-associated epigenetic alterations. We discuss the extent to which such epigenetic alterations alter susceptibility to common chronic diseases and how they might be mitigated by some nutrients, albeit within narrow margins. We conclude by discussing key issues that must be resolved if human epigenetic data is to provide useful biomarkers and mechanistic insights into how low dose chronic exposure to these metals might alter the epigenome and increase disease susceptibility.

This work was supported by NIH grants R01DK085173, P30ES025128, P01ES022831 and US EPA grant RD-83543701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the USEPA.