Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and mercury: strategies and challenges.

Paul D Ray,Rebecca C Fry,Andrew Yosim

doi:10.3389/fgene.2014.00201

Paul D Ray, Rebecca C Fry + Show 1 more

Open Access

https://doi.org/10.3389/fgene.2014.00201

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Abstract

Exposure to toxic metals poses a serious human health hazard based on ubiquitous environmental presence, the extent of exposure, and the toxicity and disease states associated with exposure. This global health issue warrants accurate and reliable models derived from the risk assessment process to predict disease risk in populations. There has been considerable interest recently in the impact of environmental toxicants such as toxic metals on the epigenome. Epigenetic modifications are alterations to an individual's genome without a change in the DNA sequence, and include, but are not limited to, three commonly studied alterations: DNA methylation, histone modification, and non-coding RNA expression. Given the role of epigenetic alterations in regulating gene and thus protein expression, there is the potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. In the present review, epigenetic alterations induced by five high priority toxic metals/metalloids are prioritized for analysis and their possible inclusion into the risk assessment process is discussed.

Highlights

Epigenetic data in the arsenic risk assessment process As a specific example demonstrating how arsenic-associated epigenetic modifications may inform the risk assessment process, we considered DNA methylation patterning in response to arsenic exposure
Differential DNA methylation profiles in immortalized cells lines transformed by chronic cadmium exposure were seen in established cancer cell lines as well as primary tumor tissues (Severson et al, 2012). These results suggest that cadmiumassociated cancers may share DNA methylation signatures and these signatures may serve as biomarkers in the risk assessment process
INTEGRATION OF EPIGENETIC DATA INTO THE RISK ASSESSMENT PROCESS The risk assessment process attempts to define associations between specific health outcomes and exposure to a specific agent, and to determine levels of exposure at which negative health outcomes associated with the exposure are minimized

Summary

Introduction

RISK ASSESSMENTThe US Environmental Protection Agency (EPA) conducts human health risk assessments for toxic chemicals using a four tier process as part of the Integrated Risk Information System (IRIS) Program (EPA, 2014a). In the context of epigenetic data that could inform human health risk assessment, an overview of epigenetic alterations in the context of five priority toxic metals and their relationship to gene expression and disease is presented.

Results

Conclusion