Coal Dust Increases Bax Expression, Increases Apoptosis, and Supresses CYP1A1 Induction in a Rat Model of Mixed Exposure to Polycyclic Aromatic Hydrocarbons and Respirable Particles

Details

• Personal Author:
  Battelli L ; Castranova, Vincent ; Ghanem M ; Hubbs, Ann F. ; Kashon ML ; Mercer RR ; Nath J ; Scabilloni JF ; Vallyathan V
• Description:
  Apoptosis has been described in lung following exposure to inflammatory agents, such as silica. The bax gene contains 2 Ah receptor response elements, suggesting a relationship between bax-mediated apoptosis and xenobiotic metabolism. Suppression of pulmonary CYP1A1 induction by coal dust (CD) exposure occurred in the rat lung. Therefore, we hypothesized that CD exposure in rat lung causes bax-mediated apoptosis and bax expression suppresses CYP1A1 induction. To explore this relationship, male Sprague-Dawley rats were intratracheally instilled with 2.5, 10, 20, and 40 mg CD/rat or vehicle (saline). On day 11, CYP1A1 was induced by intraperitoneal (IP) injection of 50 mg/kg beta-naphthoflavone (BNF). Rats were sacrificed on day 14, and lung sections were stained by immunofluorescence and morphometrically analyzed for CYP1A1, bax and an alveolar type II (AT-II) cell marker (cytokeratins 8/18). Bax expression was increased by CD in a dose-dependent manner, and CYP1A1 expression was inversely related to bax expression in AT-II cells. Since bax is a pre-apoptotic protein, we investigated the association of apoptosis with CYP1A1 suppression. Therefore, rats were injected IP with the caspase inhibitor, Q-VD-OPH or vehicle (DMSO) on days 0, 5, 9, 10, 11, 12, and 13 post CD-exposure. CYP1A1 was induced by BNF injection on day 11. Rats were sacrificed on day 14. CD exposure significantly suppressed CYP1A1 activity, increased bax expression and increased apoptosis in pulmonary cells. The injection of Q-VD-OPH significantly suppressed bax expression and apoptosis. However, the CD-mediated suppression of CYP1A1 induction was not significantly affected. These findings suggest that CD exposure suppresses CYP1A1 induction, but this suppression is not caused by bax expression or pulmonary cell apoptosis. [Description provided by NIOSH]
• Subjects:
  Animals Coal Dust Hydrocarbons Laboratories Lung Diseases Occupational Health Polycyclic Aromatic Hydrocarbons Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal-studies Coal-dust Dust-particles Dusts Exposure-levels Laboratory-animals Lung-disorders Models Polycyclic-aromatic-hydrocarbons Pulmonary-system-disorders Respirable-dust Respiratory-system-disorders Silica-dusts

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• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; 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:
  72
• Volume:
  78
• NIOSHTIC Number:
  nn:20025053
• Citation:
  Toxicologist 2004 Mar; 78(S-1):72
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
• Supplement:
  S-1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5d34a2efe3a8b881015d3ea3954329d0a73e8c60f5878c01bce254cb0fd3bf11022d5664afd026150506f2d9eb3ff5e429cd34a88ed635d9da3d11f07dddd72a
• Download URL:
  https://stacks.cdc.gov/view/cdc/196561/cdc_196561_DS1.pdf
• File Type:
  [PDF - 87.57 KB ]