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Genotoxic and epigenetic mechanisms in arsenic carcinogenicity

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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.

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Acknowledgments

Elisa Bustaffa and Fabrizio Bianchi thank the Project “Sorveglianza epidemiologica in aree interessate da inquinamento ambientale da arsenico di origine naturale o antropica”, SEpiAs—CCM 2010, funded by the Italian Ministry of Health.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Unit of Environmental Epidemiology and Diseases Registries, Institute of Clinical Physiology, National Council of Research, Via Moruzzi 1, 56123, Pisa, Italy

    Elisa Bustaffa & Fabrizio Bianchi

  2. Medical Genetics Laboratory, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy

    Andrea Stoccoro & Lucia Migliore

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  1. Elisa Bustaffa
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  2. Andrea Stoccoro
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  3. Fabrizio Bianchi
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Correspondence to Lucia Migliore.

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Elisa Bustaffa and Andrea Stoccoro have contributed equally to the manuscript.

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Bustaffa, E., Stoccoro, A., Bianchi, F. et al. Genotoxic and epigenetic mechanisms in arsenic carcinogenicity. Arch Toxicol 88, 1043–1067 (2014). https://doi.org/10.1007/s00204-014-1233-7

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