Transcriptional activation of the proto-oncogene c-jun by asbestos and H2O2 is directly related to increased proliferation and transformation of tracheal epithelial cells

Details

• Personal Author:
  Janssen YW ; Mossman BT ; Timblin CR
• Description:
  The mechanisms and role of c-jun activation in the aberrant proliferation of cells were studied. Hamster tracheal epithelial (HTE) cells were transfected with the reporter plasmid jun- luciferase and the empty expression vector Rous sarcoma virus (RSV- O). The treated cells were harvested 16 or 40 hours (hr) after exposure to crocidolite (12001284) asbestos, hydrogen-peroxide (7722841) (H2O2), or the tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA). Significantly increased luciferase activity was detected after 16 and 40hr exposure to 2.5 or 5.0 micrograms/cubic centimeter asbestos, 10 micromolar H2O2, or 100 nanograms/milliliter TPA. Confluent cultures of RSV-jun or RSV-O transfected cells were incubated in the presence of 5-bromo-2'-deoxyuridine (BrdUrd) for 8hr. A significant increase was observed in the percent of RSV-jun cells incorporating BrdUrd compared to RSV-O cells. Subsequent 16hr incubation with asbestos decreased the percentage of BrdUrd positive transfected cells relative to untreated RSV-O control cells. The percentages of BrdUrd positive RSV-jun transfectants, whether untreated, asbestos or H2O2 exposed, were significantly higher than the corresponding RSV-O transfectants. The effect of overexpression of c-jun on cell growth rates was studied by determining cell numbers of RSV-O and RSV-jun 24hr, 48hr, and 72hr after low density plating. A significant increase in the number of RSV-jun over RSV-O cells was seen only at 48hr. When this same experiment was run concurrently with asbestos exposure, a significant increase was seen in the number of RSV-jun over RSV-O cells only after 72hr. Transfected RSV-O and RSV-jun cells were plated on soft agar and incubated for 21 days. Significantly more RSV-jun colonies were observed than RSV-O transfected cell colonies. The authors conclude that asbestos and H2O2 activate AP-1-dependent gene transcription and that overexpression of c-jun in HTE cells leads to increased proliferation and cellular transformation. [Description provided by NIOSH]
• Subjects:
  Cell Division Cells, Cultured Neoplasms Occupational Exposure Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Acute-exposure Cancer Cell-cultures Cell-division Cell-growth Cell-transformation In-vitro-studies Mammalian-cells NIOSH-Grant NIOSH-Publication Respiratory-system-disorders

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• ISSN:
  0008-5472
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 1 ; Vermont
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  55
• Issue:
  13
• NIOSHTIC Number:
  nn:00227443
• Citation:
  Cancer Res 1995 Jul; 55(13):2723-2726
• Contact Point Address:
  Pathology University of Vermont Medical Alumni Bldg Burlington, VT 05405
• CAS Registry Number:
  Crocidolite asbestos (CAS RN 12001-28-4) ; Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  1995
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  University of Vermont & St Agric College, Burlington, Vermont
• Peer Reviewed:
  True
• Start Date:
  19940930
• Source Full Name:
  Cancer Research
• End Date:
  19970929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6ba3a3c0b2008254105a884c7d6441f825f4758b2570b851cdb62bc689dabc2a948dcf09157fd545b299d1e98163aeb2a11ddf9274c06fe2666ce560bbf11e59
• Download URL:
  https://stacks.cdc.gov/view/cdc/205806/cdc_205806_DS1.pdf
• File Type:
  [PDF - 971.30 KB ]