Oncogenomic disruptions in arsenic-induced carcinogenesis.
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.
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Adam P
AP
Sage
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Brenda C
BC
Minatel
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Kevin W
KW
Ng
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Greg L
GL
Stewart
Centre of Excellence in Cancer Prevention, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Trevor J B
TJB
Dummer
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Wan L
WL
Lam
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Victor D
VD
Martinez
D000818:Animals; D001151:Arsenic / Q000009:adverse effects*; D063646:Carcinogenesis / Q000139:chemically induced*; D002869:Chromosome Aberrations / Q000139:chemically induced; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000187:drug effects; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D022661:RNA, Untranslated / Q000235:genetics
D022661:RNA, Untranslated; D001151:Arsenic
arsenic; cancer; epigenetics; genetics; non-coding RNA