Arsenic-Induced Gene Expression in Urinary Bladder Epithelium

Details

• Personal Author:
  Hulderman T ; Luster MI ; Simeonova PP ; Wang S
• Description:
  Occupational and environmental exposure to arsenic has been related by epidemiological studies to development of skin and urinary bladder cancer. Although the mechanisms of arsenic carcinogenesis have not been defined, increasing evidence indicates the role of epigenetic mechanisms, including modulation of signaling pathways of cell growth. We demonstrated that arsenic exposure is associated with tissue accumulation of inorganic, and to lesser extent dimethylarsenicacid, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. The arsenic accumulation in urinary bladder tissue and AP-1 activation demonstrated dose-dependence and strong correlation. That was supported also by recovery studies. Arsenic levels as well as AP-1 binding started to decrease significantly after 8 weeks of recovery period. Consistent with the in vivo data, arsenic induced sustained MAP kinase and AP-1 activation in uroepithelial cell line. Arsenic-triggered epidermal growth factor receptor phosphorylation was involved but it was not initiation event of MAP kinase cascade. Gene expression studies using cDNA microarays, RNase protection assay, and reverse transcription - PCR indicated that arsenic alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-l, as well as cell arrest, such as GADD153 and GADD45. Arsenic - induced gene expression might contribute to carcinogenesis in urinary bladder by dysregulation of the cell cycle events. [Description provided by NIOSH]
• Subjects:
  Arsenic Carcinogens Environmental Exposure Epidemiology Genetics Inorganic Chemicals Neoplasms Occupational Exposure Occupational Health Safety Skin Skin Diseases Urogenital Diseases Urogenital System

  More +
• Keywords:
  Arsenic-compounds Bladder-cancer Bladder-disorders Cancer Carcinogenesis Cell-growth Environmental-exposure Genes In-vivo-studies Occupational-exposure Skin-cancer

  More +
• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20021450
• Citation:
  Toxicologist 2001 Mar; 60(1):204
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ad7f90ec81ea5804b2a519c1ce025c69475fa503e8993634ed318869e1211eb655b70ea07b1eebc2f67296263bbc791e03b17f420ec1f09ca490e691330746c0
• Download URL:
  https://stacks.cdc.gov/view/cdc/198761/cdc_198761_DS1.pdf
• File Type:
  [PDF - 117.01 KB ]