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Review
. 2014 Jul 16:5:201.
doi: 10.3389/fgene.2014.00201. eCollection 2014.

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

Paul D Ray  1 , Andrew Yosim  2 , Rebecca C Fry  1
Affiliations
Review

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

Paul D Ray et al. Front Genet. .

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.

Keywords: DNA methylation; disease; epigenetics; epigenomics; histone modification; miRNA; risk assessment.

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Figures

Figure 1
Figure 1
The role of the epigenome in toxic metal-induced disease pathways. Epigenetic alterations classified broadly as effects to the “epigenome” have the potential to regulate mRNAs/transcripts (i.e., the transcriptome) and ultimately impact protein expression (i.e., the proteome) within cells. Exposure to toxic metals can impact various components of the epigenetic machinery. These toxic metal-mediated epigenetic alterations may directly impact gene transcription and subsequently regulate protein translation, leading to aberrant expression of key mediators of disease processes.
Figure 2
Figure 2
Incorporating epigenetic data into the risk assessment process. Epigenetic data may be used to inform each component of the risk assessment process. The risk assessment process consists of four key steps (A, left box); hazard identification, dose-response assessment, exposure assessment, and risk characterization. The intent of each step is met by applying clinical and epidemiological data to the criteria of each step (A, right box). Epigenetic data can be used to inform the risk assessment process by the integration of key data into the criteria framework (B) of each step in the process.
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