Asbestos Induces Nuclear Factor Kappa B (NF-Kappa B) DNA-Binding Activity and NF-Kappa B-Dependent Gene Expression in Tracheal Epithelial Cells

Details

• Personal Author:
  Barchowsky A ; Driscoll KE ; Janssen YM ; Mossman BT ; Treadwell M
• Description:
  The effects of asbestos (1332214) on nuclear-factor-kappa-B (NF- kappa-B) DNA binding activity and NF-kappa-B dependent gene expression were examined. Hamster tracheal epithelial (HTE) cells were cultured with crocidolite (12001284) concentrations of 1.25 or 5 micrograms per square centimeter (microg/cm2) for up to 24 hours. Following exposure, nuclear protein extracts were analyzed for enhanced NF-kappa-B DNA binding activity using a gel mobility shift assay. Transfection studies using the calcium phosphate coprecipitation technique were conducted in order to measure NF- kappa-B dependent gene expression. Messenger RNA (mRNA) levels of c- myc, a gene regulated by NF-kappa-B, were determined via Northern blot analysis. Multiple gel shift complexes, competitively blocked by excesses of NF-kappa-B, were observed in the nuclear protein extracts of crocidolite exposed HTE cells. Antibodies recognizing the p50 and p65 members of the NF-kappa-B family also reduced the formation of gel shift complexes. Crocidolite exposure caused a dose dependent increase in complex formation. Pretreatment of HTE cells with N-acetyl-L-cysteine, a glutathione stimulator, induced a significant decrease in the crocidolite induced NF-kappa-B DNA binding activity. The expression of NF-kappa-B dependent genes was increased in HTE cells transfected with an NF-kappa-B consensus sequence and exposed to lipopolysaccharide for 4 or 16 hours or crocidolite for 16 hours. Levels of c-myc mRNA were significantly elevated in HTE cells exposed to crocidolite for 4 to 24 hours. The authors conclude that asbestos induces NF-kappa-B DNA binding activity and NF-kappa-B dependent gene expression, both of which may be involved in the development of asbestos induced lung cancers. [Description provided by NIOSH]
• Subjects:
  Asbestos Cells, Cultured DNA Genetics Inorganic Chemicals Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Asbestos-fibers Cell-cultures Deoxyribonucleic-acids Dose-response Exposure-levels Genetic-factors Lung-cells NIOSH-Grant NIOSH-Publication Pulmonary-system-disorders Ribonucleic-acids

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• ISSN:
  0027-8424
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New Hampshire ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  92
• Issue:
  18
• NIOSHTIC Number:
  nn:00241559
• Citation:
  Proc Natl Acad Sci U.S.A. 1995 Aug; 92(18):8458-8462
• Contact Point Address:
  Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  1995
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  Dartmouth College, Hanover, New Hampshire
• Peer Reviewed:
  True
• Start Date:
  19940930
• Source Full Name:
  Proceedings of the National Academy of Sciences of the United States of America
• End Date:
  19960929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:54bb909e8ad377161096b96c10ebee920588d410106b3535e3835d4ae1fef11ff73b4fa020665c64572f59afe97c34ab66dae673e596d85e0513ff931638d5c6
• Download URL:
  https://stacks.cdc.gov/view/cdc/198103/cdc_198103_DS1.pdf
• File Type:
  [PDF - 1.32 MB ]