Oncogenomic disruptions in arsenic-induced carcinogenesis.

Adam P Sage,Wan L Lam,Kevin W Ng,Trevor J.B Dummer,Victor D Martinez,Greg L Stewart,Brenda C Minatel

doi:10.18632/oncotarget.15106

Adam P Sage, Wan L Lam + Show 5 more

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https://doi.org/10.18632/oncotarget.15106

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Abstract

Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process.

Highlights

Arsenic is an environmental carcinogen associated with human skin, bladder, liver and lung cancers [1, 2]
As literature relatinggenetics to arsenic exposure has been accumulating at an increasing rate (Figure 3), we review the latest advances in the oncogenomic effects of arsenic-induced carcinogenesis
Clinical implications of the prevalence of arsenic groundwater contamination are evidenced by an impact on the incidence of cancer, even at low exposure levels [154]

Summary

Introduction

Arsenic is an environmental carcinogen associated with human skin, bladder, liver and lung cancers [1, 2]. Arsenic exposure has been shown to induce global DNA hypomethylation, as well as specific gene promoter methylation changes through the alteration of CpG methylation status [90]. IAs exposure was observed to be a putative cause of significant DNA hypomethylation in adult peripheral blood mononuclear cells, suggesting possible involvement in lymphatic cancers [97].

Results

Conclusion