Coal Dust Alters β-Naphthoflavone-Induced Aryl Hydrocarbon Receptor Nuclear Translocation in Alveolar Type II Cells

Details

• Journal Article:
  Particle and Fibre Toxicology
• Personal Author:
  Ghanem, Mohamed M. ; Battelli, Lori A. ; Law, Brandon F. ; Castranova, Vincent ; Kashon, Michael L. ; Nath, Joginder ; Hubbs, Ann F.
• Description:
  Background: many polycyclic aromatic hydrocarbons (PAHs) can cause DNA adducts and initiate carcinogenesis. Mixed exposures to coal dust (CD) and PAHs are common in occupational settings. In the CD and PAH-exposed lung, CD increases apoptosis and causes alveolar type II (AT-II) cell hyperplasia but reduces CYP1A1 induction. Inflammation, but not apoptosis, appears etiologically associated with reduced CYP1A1 induction in this mixed exposure model. Many AT-II cells in the CD-exposed lungs have no detectable CYP1A1 induction after PAH exposure. Although AT-II cells are a small subfraction of lung cells, they are believed to be a potential progenitor cell for some lung cancers. Because CYP1A1 is induced via ligand-mediated nuclear translocation of the aryl hydrocarbon receptor (AhR), we investigated the effect of CD on PAH-induced nuclear translocation of AhR in AT-II cells isolated from in vivo-exposed rats. Rats received CD or vehicle (saline) by intratracheal (IT) instillation. Three days before sacrifice, half of the rats in each group started daily intraperitoneal injections of the PAH, beta-naphthoflavone (BNF). Results: fourteen days after IT CD exposure and 1 day after the last intraperitoneal BNF injection, AhR immunofluorescence indicated that proportional AhR nuclear expression and the percentage of cells with nuclear AhR were significantly increased in rats receiving IT saline and BNF injections compared to vehicle controls. However, in CDexposed rats, BNF did not significantly alter the nuclear localization or cytosolic expression of AhR compared to rats receiving CD and oil. Conclusion: our findings suggest that during particle and PAH mixed exposures, CD alters the BNFinduced nuclear translocation of AhR in AT-II cells. This provides an explanation for the modification of CYP1A1 induction in these cells. Thus, this study suggests that mechanisms for reduced PAH-induced CYP1A1 activity in the CD exposed lung include not only the effects of inflammation on the lung as a whole, but also reduced PAHassociated nuclear translocation of AhR in an expanded population of AT-II cells. [Description provided by NIOSH]
• Subjects:
  Aerosols Air Pollutants, Occupational Animals Coal Dust Environmental Monitoring Hazardous Substances Hydrocarbons Laboratories Lung Lung Diseases Microbiology Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Workplace

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• Keywords:
  Aerosol-particles; Airborne-particles; Animals; Biohazards; Biological-effects; Breathing; Breathing-atmospheres; Cell-function; Cell-morphology; Cellular-function; Cellular-reactions; Coal-dust; Dust-exposure; Dust-inhalation; Dust-particles; Exposure-assessment; Exposure-levels; Exposure-methods; Hydrocarbons; Laboratory-animals; Laboratory-testing; Lung; Lung-irritants; Microbiology; Microscopic-analysis; Molecular-biology; Particulate-dust; Particulates; Particulate-sampling-methods; Pulmonary-congestion; Pulmonary-function; Pulmonary-system; Respirable-dust; Toxic-effects; Toxic-materials; Workplace-studies
• Source:
  Part Fibre Toxicol 2009 Aug; 6:21
• ISSN:
  1743-8977
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Pages in Document:
  12 pdf pages
• Volume:
  6
• NIOSHTIC Number:
  nn:20035746
• Contact Point Address:
  Dr. Ann Hubbs, Pathology and Physiology Research Branch, Health Effect Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV, 26505
• Email:
  Ahubbs@cdc.gov
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health CDC Public Access
• Main Document Checksum:
  urn:sha-512:df441cc92aad1021f2fe9bca58f1fc346aad8acc72e3dcb0fa76f063906adb214d018d15820da075fe13fd95f9afeeefaf7cf4390195840078607f67715100ca
• Download URL:
  https://stacks.cdc.gov/view/cdc/3653/cdc_3653_DS1.pdf
• File Type:
  [PDF - 3.70 MB ]