Quantitative Relationship Between Arsenic Exposure and AP-1 Activity in Mouse Urinary Bladder Epithelium

Details

• Personal Author:
  Crecelius E ; Kashon ML ; Kommineni C ; Luster MI ; Simeonova PP ; Wang S
• Description:
  Because of the potential of arsenic for causing cancer in humans, and of the fact of widespread environmental and occupational exposure, deriving acceptable human-limit values has been of major concern to industry as well as to regulatory agencies. Based upon epidemiological evidence and mechanistic studies, it has been argued that a non-linear dose-response model at low-level exposures is more appropriate for calculating risk than the more commonly employed linear-response models. In the present studies, dose-response relationships and recovery studies employing a cancer precursor marker, i.e., activating protein (AP)-1 DNA-binding activity, were examined in bladders of mice exposed to arsenic in drinking water and compared to histopathological changes and arsenic tissue levels in the same tissue. While AP-1 is a functionally pleomorphic transcription factor regulating diverse gene activities, numerous studies have indicated that activation of the MAP kinase pathway and subsequently increased AP-1 binding activities, is a precursor for arsenic-induced cancers of internal organs as well as the skin. We observed previously that within 8 weeks of exposure AP-1 activation occurs in urinary bladder tissue of mice exposed to arsenic in the drinking water. In the present studies, C57BL/6 mice were exposed to sodium arsenite at various concentrations in the drinking water for 8 consecutive weeks. Minimal but observable AP-1 activity occurred in bladder tissue at exposure levels below which histopathological changes or arsenic tissue accumulation was detected. Marked AP-1 DNA-binding activity only occurred at exposure levels of sodium arsenite above 20 microg/ml, where histopathological changes and accumulation of arsenic in the urinary bladder epithelium occurred. Although the experimental design did not allow statistical modeling of the entire dose-response curve, the general shape of the dose-response curve is not inconsistent with the previously proposed hypothesis that arsenic-induced cancer follows a non-linear dose-response model. [Description provided by NIOSH]
• Subjects:
  Arsenic Environmental Exposure Inorganic Chemicals Neoplasms Occupational Exposure Occupational Health Risk Assessment Safety
• Keywords:
  Arsenic-compounds Author Keywords: Falls Balance Control Cancer Environmental-exposure Exposure-levels Occupational-exposure Occupational Injury Risk-analysis Visual References;
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; 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:
  279-284
• Volume:
  60
• Issue:
  2
• NIOSHTIC Number:
  nn:20021875
• Citation:
  Toxicol Sci 2001 Apr; 60(2):279-284
• Contact Point Address:
  Toxicology and Molecular Biology Branch, Biostatistics Branch, and Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
• Email:
  mluster@cdc.gov
• Federal Fiscal Year:
  2001
• NORA Priority Area:
  Research Tools and Approaches: Risk Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7f8b5e804cfb1f59b69e7f57e5390463bc8d5046ddca26cbbf050330185c0c6b64c28e6baa8b9ff97c5fb7dbd27217ee851fd3e21a9ff7f4cc86cdb81354d416
• Download URL:
  https://stacks.cdc.gov/view/cdc/198962/cdc_198962_DS1.pdf
• File Type:
  [PDF - 330.07 KB ]