Arsenic Exposure and Epigenetic Modification: An Updated Systematic Review of Epidemiological Findings


Xuefeng Ren
Robert Adams
Lillian Collins
Nehel Verma
Theresa Williams


Inorganic arsenic exposure; Epigenetic mechanisms; DNA methylation; Histone Modification; MicroRNA, Human epidemiologic investigation


Inorganic arsenic exposure is a global public health concern. It is believed that the dysregulation of epigenetic mechanisms contributes and plays a major role in arsenic associated adverse health effects.  Previously, we conducted a systematic review that summarized the findings of arsenic-induced epigenetic disruptions from in vitro and animal studies. In recent years, there has been an increasing number of studies conducted in humans becoming available.  In an effort to further clarify the association between arsenic exposure and epigenetic modifications, here, we reviewed the effects of arsenic on the epigenetic mechanisms, including DNA methylation, histone post-translational modification, and altered miRNA levels in studies conducted in human populations.  Our systematic review reveals that in humans exposed to arsenic, global DNA methylation appears to increase, which is contrary to in vitro and majority animal studies. Specific genes that were identified as having their methylation profile altered by arsenic exposure were associated with various cancer and non-cancer diseases. The histone modifications post arsenic exposure in humans are more diverse and amino acid specific.   Arsenic exposure changes the expression of specific miRNAs in human studies. Overall, it is consistent that exposure to arsenic leads to alterations of epigenetic mechanisms among almost all human studies; however, current studies do not seem to identify conserved epigenetic biomarkers across studies.  Further studies are warranted with standardized study design, clearly defined outcomes of health effects, and measurements of arsenic exposure.  


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