EPA Science Inventory

Arsenic and the Epigenome: Linked by Methylation(SOT)

Citation:

Bailey, K. A., L. Smeester, W. O. WARD, J. Rager, X. Guan, N. Smith, G. Garcia-Vargas, L. Del-Razo, Z. Drobna, M. Stylbo, AND R. Fry. Arsenic and the Epigenome: Linked by Methylation(SOT). Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.

Description:

Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically-exposed individuals are susceptible to arsenic poisoning, or arsenicosis. In some exposed populations arsenicosis susceptibility is dependent in part on the ability of individuals to biotransform iAs to monomethylated and dimethylated arsenic species (MMAs and DMAs, respectively). In many exposed populations increased risk of several arsenic-associated diseases is observed in individuals with high ratios of MMAs to DMAs in their urine. In this study we set out to examine relationships between genomic DNA methylation status, iAs biotranformation capacity, and arsenicosis in chronically-exposed individuals from Zimapan, Hildago, Mexico. Using a state-of-the-art technique to map the methylomes of our study subjects, we identified a large interactome of hypermethylated genes in arsenicosis subjects that are enriched for their involvement in arsenic-associated diseases such as cancer, heart disease, and diabetes. Notably, we have uncovered an arsenic-induced tumor suppressorome, a complex of 17 tumor suppressors known to be silenced in human cancers. We also found that urinary concentrations of individual arsenic species were associated with distinct DNA methylation patterns. In particular, we found that the promoter methylation patterns of genes associated with type I diabetes mellitus and cancer development were dependent on urinary ratios of MMAs lOMAs and DMAs+MMAs/iAs. In addition, increased concentrations of all arsenicals tested were correlated with differential methylation of histone deacetylase gene promoters, suggesting arsenic exposure may impact multiple components of the epigenome. Together, these findings suggest a possible epigenetic mode of arsenic-induced disease. [This abstract does not reflect EPA policy.]

Purpose/Objective:

Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically-exposed individuals are susceptible to arsenic poisoning, or arsenicosis. In some exposed populations arsenicosis susceptibility is dependent in part on the ability of individuals to biotransform iAs to monomethylated and dimethylated arsenic species (MMAs and DMAs, respectively).

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Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Start Date: 03/15/2011
Completion Date: 03/15/2011
Record Last Revised: 11/19/2012
Record Created: 10/08/2011
Record Released: 10/08/2011
OMB Category: Other
Record ID: 238808

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ASSOCIATE DIRECTOR FOR HEALTH

RESEARCH CORES UNIT