Effects of arsenic exposure on DNA methylation and epigenetic gene regulation.
Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed to activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in the activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well as areas where consistencies and inconsistencies exist.
Reichard
John F
JF
Department of Environmental Health & Center for Environmental Genetics, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, OH 45267-0056, USA. John.Reichard@uc.edu
Puga
Alvaro
A
D000818:Animals; D001149:Arsenates / Q000378:metabolism; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000503:physiopathology; D009747:Nutritional Physiological Phenomena / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*
D001149:Arsenates; D008780:Methyltransferases; D001151:Arsenic; C025657:arsenic acid