Epigenetic Changes in Individuals with Arsenicosis

Smeester, Lisa; Rager, Julia E.; Bailey, Kathryn A.; Guan, Xiaojun; Smith, Nicola; Garcı́a-Vargas, Gonzalo G.; Razo, Luz M. Del; Drobná, Zuzana; Kelkar, Hemant; Stýblo, Miroslav; Fry, Rebecca C.

doi:10.1021/tx1004419

Cited by 154 publications

(120 citation statements)

References 13 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…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).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Arsenic Speciation and Quantification in Human Urothelial and Hepatic Cells

Zdrenka¹,

Hippler²,

Johnen³

et al. 2012

Bladder Cancer - From Basic Science to Robotic Surgery

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Intracellular Arsenic Speciation and Quantification in Human Urothelial and Hepatic Cells

Zdrenka¹,

Hippler²,

Johnen³

et al. 2012

Bladder Cancer - From Basic Science to Robotic Surgery

View full text Add to dashboard Cite

“…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). …”

Section: Temporal Relationships Between Stressorsmentioning

confidence: 99%

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

Solomon

Wilks

Bachman

et al. 2016

Critical Reviews in Toxicology

View full text Add to dashboard Cite

When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a ''problem formulation'' phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as ''modulating factors'' (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

show abstract

“…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.…”

Section: Epigenomics Examplementioning

confidence: 99%