Activation of Activator Protein-1 by Reactive Oxygen Species Associated with Asbestos

Details

• Personal Author:
  Castranova, Vincent ; Ding M ; Shi X ; Vallyathan V
• Description:
  Inhalation of asbestos causes alterations in cell signaling cascades, gene expression, cell injury and cell proliferation which may lead to pulmonary fibrosis, lung cancer, or mesothelioma. Asbestos-mediated free radical reactions are believed to trigger a number of cellular and molecular events that may promote fibrogenesis and carcinogenesis. Because activator protein I (AP-1) plays an important role in pre-neoplastic-to-neoplastic transformation tumor promotion and metastatsis, we studied the possible activation of AP-1 in vitro in cultured JB6 cells and in vivo using transgenic mice after exposure to crocidolite asbestos caused a significant (22-fold) activation of AP-1 in bronchiolar tissue compared to a moderate 10-fold increase in the lung tissue. The induction of AP-1 in asbestos exposure appears to be mediated through the phosphorylation of mitogen-activated protein kinases, Erk 1 and Erk 2. Hydroxyl radical scavengers inhibited asbestos-induced AP-1 activation. These data support the hypothesis that oxygen radical mechanisms may be associated with pulmonary fibrosis and carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Animals Asbestos Carcinogens Dust Fibrosis Free Radicals Inorganic Chemicals Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Animal Studies Asbestos Dust Asbestosis Carcinogenesis Carcinogenicity Fibrogenesis Fibrogenicity Free Radicals Inhalation Studies In Vitro Studies In Vivo Studies Laboratory Animals Lung Cancer Pulmonary System Disorders Respiratory System Disorders

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• ISSN:
  1096-6080
• 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
• Volume:
  54
• Issue:
  1
• NIOSHTIC Number:
  nn:20021084
• Citation:
  Toxicologist 2000 Mar; 54(1):254
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2f6ff909ae57a7490a8881e54258fa87c7a388b1ba7930bcd7db5ff6bac71a4b5fe97d5e65e376ff2817556787245e166d02cd31df2df44f120d3bff72c093b5
• Download URL:
  https://stacks.cdc.gov/view/cdc/198642/cdc_198642_DS1.pdf
• File Type:
  [PDF - 204.68 KB ]