As(III) Transcriptionally Activates the gadd45a Gene via the Formation of H2O2

Details

• Personal Author:
  Bower JJ ; Chen F ; Leonard, Stephen S. ; Shi X
• Description:
  Arsenic is a ubiquitous environmental contaminant associated with increased risks of human cancers of the skin, lung, bladder, and prostate. Intriguingly, it is also used to treat certain types of leukemia. It has recently been suggested that these paradoxic effects may be mediated by arsenic's ability to simultaneously activate DNA damage and apoptotic and transformation pathways. Here, we investigate the effects of arsenic exposure on the induction of the growth arrest and DNA damage protein 45a (GADD45a), which is thought to play roles in apoptosis, DNA damage response, and cell cycle arrest. We found that arsenic transcriptionally activates the gadd45a promoter located in a 153-bp region between -234 and -81, relative to the transcriptional start site. In addition, this transcriptional induction was abrogated in the presence of H2O2 scavengers, suggesting a role for H2O2 in the transcriptional control of the gadd45a gene through a Fenton-like free radical mechanism. [Description provided by NIOSH]
• Subjects:
  Arsenic DNA Environmental Pollution Genetics Inorganic Chemicals Lung Lung Diseases Neoplasms Occupational Health Poisoning Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Skin Skin Diseases Urogenital Diseases Urogenital System

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• Keywords:
  Arsenic-compounds Arsenic-poisoning Arsenites Bladder-cancer Cancer DNA-damage Environmental-contamination Genes Lung-cancer Prostate-cancer Risk-analysis Risk-factors Skin-cancer

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• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  285-294
• Volume:
  41
• Issue:
  2
• NIOSHTIC Number:
  nn:20030626
• Citation:
  Free Radic Biol Med 2006 Jul; 41(2):285-294
• Email:
  xshi@cdc.gov
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Free Radical Biology and Medicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bba545f026bf3adfd7ec3c80a994adfcd41900a3da0cff878b258da415162ae12bf2572c9f42528faab7d34c3440142c63f924b6e68b79b4094bcba8244195b8
• Download URL:
  https://stacks.cdc.gov/view/cdc/191171/cdc_191171_DS1.pdf
• File Type:
  [PDF - 425.92 KB ]