Epigenetic Changes in Individuals with Arsenicosis

Abstract

Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically exposed individuals are susceptible to arsenicosis or arsenic poisoning. Using a state-of-the-art technique to map the methylomes of our study subjects, we identified a large interactome of hypermethylated genes 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. This finding represents a pivotal clue in unraveling a possible epigenetic mode of arsenic-induced disease.

Intracellular Arsenic Speciation and Quantification in Human Urothelial and Hepatic Cells

“…Inorganic arsenic and its metabolites are also known to be potent epigenetic modulators leading to (tissue specific) altered cellular functions, malignant transformation and tumorigenesis. Many studies report arsenic induced aberrant DNA methylation patterns (Sutherland & Costa, 2003;Smeester et al, 2011;Ren et al;, resulting in changes in the promoter activity that lead to altered gene expression (Jensen et al, 2009). Aberrant DNA methylation patterns might be the result of arsenic-induced altered global histone modification finally leading to, among others, the silencing of tumour suppressor genes (Zhou et al, 2008).…”

Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans

“…Recovery may be very rapid (hours), such as for carbamylated AChE, longer (days-weeks) for phosphorylated/ aged AChE, or even transgenerational, such as for some genetic or epigenetic changes that modify TD or TK. This last point is important as stressors, such as famine, have resulted in epigenetic changes in humans that may affect interactive response in one generation (Koturbash et al 2011;Maze et al 2011;Smeester et al 2011) or be transgenerational (Anway et al 2005;Painter et al 2006;Skinner et al 2011;Vanhees et al 2011). …”

The Application of Omics Technologies to the Study of Mammalian Toxicology

“…While inorganic arsenic is a well-documented genotoxic agent, it may also act through epigenetic mechanisms, specifically DNA methylation, to elicit its toxicity phenotype. In order to explore the potential impact on arsenic exposure on genome-wide DNA methylation, Fry and colleagues used a ChIP-CHIP approach to evaluate the methylation of CpG islands surrounding approximately 14 000 genes using peripheral blood lymphocyte DNA from a total of 16 individuals (eight with symptoms of arsenic poisoning/arsenicosis and eight without symptoms) [60]. A total of 183 genes was associated with differentially methylated CpG islands, nearly all of which were hypermethylated in the arsenicosis group.…”