Arsenic-Induced Mitogenic Cell Signaling Pathways

Details

• Personal Author:
  Simeonova P
• Description:
  Environmental or occupational exposure to arsenic is associated with a greatly increased risk of skin, urinary bladder and respiratory tract cancers in arseniasis-endemic areas throughout the world. We have employed in vitro and in vivo models to examine the effects of arsenic on the urinary bladder epithelium. Mice exposed to 0.01 percent sodium arsenite in the drinking water demonstrated marked hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. The response was accompanied with accumulation of arsenic and induction of activating protein-1 (AP-1) in the urinary bladder tissue. Furthermore, arsenic induced activation of major mitogenic mediators, such as epidermal growth factor receptor (EGFR) and extracellular signal-regulated protein kinase (ERK), in the uropeithelium. This response is also accompanied with increased levels of non-receptor tyrosine kinase c-Src interacting with the EGFR. Consistent with these in vivo observations, arsenic activates c-Src in a human uroepithelial cell line. Using pharmacological and genetic inhibition of Src, we found that c-Src activity is a prerequisite for EGFR and ERK activation in these cells. In conclusion, arsenic shares many properties of tumor promoters by affecting specific cell signal transduction pathways responsible for cell proliferation of initiated cells or increasing the mutational rate. [Description provided by NIOSH]
• Subjects:
  Arsenic Environmental Exposure Environmental Health Environmental Pollution Metals Metals, Heavy Neoplasms Occupational Exposure Occupational Health Poisoning Respiratory Tract Diseases Safety Skin Skin Diseases Urogenital Diseases Urogenital System

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• Keywords:
  Arsenates Arsenic-poisoning Bladder-cancer Bladder-disorders Cell-alteration Cell-damage Cell-morphology Environmental-exposure Environmental-hazards Environmental-health Heavy-metal-poisoning Heavy-metals In-vitro-study In-vivo-study Occupational-exposure Occupational-hazards Occupational-health Respiratory-system-disorders Skin-cancer Skin-disorders Urogenital-system Urogenital-system-disorders

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• Publisher:
  Indian Institute of Chemical Biology
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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:
  6
• NIOSHTIC Number:
  nn:20027661
• Citation:
  Proceedings of the 28th Annual Conference and Special Symposium on Arsenic Contamination in Ground Water and its Health Effects, February 14-16, 2003. Jadavpur, India: Indian Institute of Chemical Biology, 2003 Feb; :6
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the 28th Annual Conference and Special Symposium on Arsenic Contamination in Ground Water and its Health Effects, February 14-16, 2003
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:73adb315c16a8f152702823889ed1e3078790688bcdd6962a966ee4a0723800386d1f7adfb1d2b6394cef2bad9e1a9074be4565d6206df439721f86f3fc8bafc
• Download URL:
  https://stacks.cdc.gov/view/cdc/197612/cdc_197612_DS1.pdf
• File Type:
  [PDF - 180.05 KB ]