Asbestos Induces AP-1 Activation in Cell Culture and Transgenic Mice

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Ding M ; Dong ZG ; Ma VY ; Pack D ; Shi XL ; Vallyathan V ; Ye JP
• Description:
  Occupational exposure to asbestos is linked to increased incidence of lung cancer. To investigate the carcinogenic mechanism of asbestos, activation of activator protein (AP-1) by crocidolite asbestos was examined in both a stable AP-1-luciferase reporter plasmid-transfected JB6 p+ cell line and AP-1-luciferase reporter transgenic mice. In the cultured cells asbestos caused a dose-dependent induction of AP-1 activation. The elevated AP-1 activity persisted at least for 48 hours. Asbestos also induced AP-1 transactivation in transgenic mice. AP-1 activation was observed at 2 days after exposure of the mice to asbestos via intratracheal instillation. At 3 days post-exposure, the AP-1 was elevated 10-fold in the lung tissue and 22-fold in bronchial tissue as compared to their controls. This finding is consistent with previous reports showing that asbestos causes site specific bronchogenic carcinoma. The induction effect of asbestos-induced AP-1 activity appeared to be mediated through the activation of MAP kinase family members, including extracellular signal-regulated protein kinases, Erk1 and Erk2. Aspirin inhibited asbestos-induced AP-1 activity in JB6 cells. Pretreatment of the mice with aspirin also inhibited asbestos-induced AP-1 activation. The data suggest that further investigation of the involvement of AP-1 in asbestos-induced cell proliferation and carcinogenesis as well as the potential therapeutic/preventative actions of aspirin in asbestos-induced carcinogenesis is warranted. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Asbestos Carcinogens Cells, Cultured Dust Environmental Monitoring Hazardous Substances Inorganic Chemicals Laboratories Neoplasms Occupational Health Respiratory Tract Diseases Safety

  More +
• Keywords:
  Analytical-methods Analytical-processes Animal-studies Asbestos-dust Asbestos-fibers Asbestos-products Cancer Carcinogenesis Carcinogenicity Cell-cultures Cell-damage Cell-function Cellular-function Cellular-reactions Exposure-assessment Laboratory-animals Pulmonary-system-disorders Respiratory-system-disorders Statistical-analysis Toxic-effects Toxins

  More +
• ISSN:
  0143-3334
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  40
• Issue:
  8
• NIOSHTIC Number:
  nn:20028110
• Citation:
  Carcinogenesis 1999 Mar; 40(8):351
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Aspirin (CAS RN 50-78-2)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  Carcinogenesis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:64cf4ffe2dc3bb35511543cbd55e404d97d5516a2483523fcd23393f9186fca2358daf08249b2cc668f2e8331ae9959a8595a351c3ff8a08a7b12f6c66ceabd5
• Download URL:
  https://stacks.cdc.gov/view/cdc/189782/cdc_189782_DS1.pdf
• File Type:
  [PDF - 405.84 KB ]