title: Genotoxic and epigenetic mechanisms in arsenic carcinogenicity.
abstract: Arsenic is a human carcinogen with weak mutagenic properties that induces tumors through mechanisms not yet completely understood. People worldwide are exposed to arsenic-contaminated drinking water, and epidemiological studies showed a high percentage of lung, bladder, liver, and kidney cancer in these populations. Several mechanisms by which arsenical compounds induce tumorigenesis were proposed including genotoxic damage and chromosomal abnormalities. Over the past decade, a growing body of evidence indicated that epigenetic modifications have a role in arsenic-inducing adverse effects on human health. The main epigenetic mechanisms are DNA methylation in gene promoter regions that regulate gene expression, histone tail modifications that regulate the accessibility of transcriptional machinery to genes, and microRNA activity (noncoding RNA able to modulate mRNA translation). The "double capacity" of arsenic to induce mutations and epimutations could be the main cause of arsenic-induced carcinogenesis. The aim of this review is to better clarify the mechanisms of the initiation and/or the promotion of arsenic-induced carcinogenesis in order to understand the best way to perform an early diagnosis and a prompt prevention that is the key point for protecting arsenic-exposed population. Studies on arsenic-exposed population should be designed in order to examine more comprehensively the presence and consequences of these genetic/epigenetic alterations.
authors.affiliation: Unit of Environmental Epidemiology and Diseases Registries, Institute of Clinical Physiology, National Council of Research, Via Moruzzi 1, 56123, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bustaffa
authors.forename: Andrea
authors.initials: A
authors.lastname: Stoccoro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D035683:MicroRNAs / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods
chemical_list: D002273:Carcinogens; D006657:Histones; D035683:MicroRNAs; D001151:Arsenic