Proposed Mechanisms for Arsenic Carcinogenicity: Implications for the Shape of the Dose-Response Curve

Details

• Personal Author:
  Luster M
• Description:
  Epidemiological studies have established that inorganic arsenic is a significant human carcinogen that causes tumors predominantly in the skin and bladder following oral exposure and in the lung following inhalation. Despite numerous experimental studies and proposed hypotheses, there is no consensus on arsenic's mechanism of action. It does not behave as most classical chemical carcinogens, including other metals such as cadmium or chromium. In this respect, it does not induce bacterial or mammalian cell mutations at relevant concentrations nor does it produce tumors in standard one- or two-stage animal bioassays. Recent advances have allowed development of atypical rat or mouse models for arsenic carcinogenesis. These, in conjunction with in vitro studies, have suggested that arsenic may be inducing carcinogenesis by one or more mechanisms including it's ability to cause global hypomethylation leading to heritable changes in gene expression, act as a 'comutagen' by inhibiting DNA repair, to induce chronic growth signaling through persistent activation of the MAPKinase pathway and induce oxidative damage through formation of dimethylarsenic radicals. Such mechanisms suggest the likelihood that the dose-response for arsenic may be non-linear in the low dose region and evoke the possibility that such events as genomic instability and by-stander effects may be involved. [Description provided by NIOSH]
• Subjects:
  Animals Arsenic Cadmium Carcinogens Chromium Epidemiology Inorganic Chemicals Laboratories Lung Diseases Neoplasms Occupational Health Safety

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• Keywords:
  Animal-studies Arsenic-compounds Cadmium-compounds Cadmium-dust Carcinogenicity Chromium-compounds Exposure-levels In-vitro-studies Laboratory-animals Lung-disorders Models Tumors

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• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  112-113
• Volume:
  72
• NIOSHTIC Number:
  nn:20022665
• Citation:
  Toxicologist 2003 Mar; 72(S-1):112-113
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Chromium (CAS RN 7440-47-3)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2f047952c55999724af8983e9582938377c8886b501e088f87425d0952ae2d1aa9aeef5cc39324945f032243060c06cd0330ca357afff6aaf6eb2224181e47a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/199360/cdc_199360_DS1.pdf
• File Type:
  [PDF - 61.30 KB ]