Respirable Coal Dust Particles Modify Cytochrome P4501A1 (CYP1A1) Expression in Rat Alveolar Cells

Details

• Personal Author:
  Barger MW ; Battelli LA ; Castranova, Vincent ; Ghanem MM ; Hubbs, Ann F. ; Kashon ML ; Ma JY ; Nath J ; Porter, Dale ; Vallyathan V
• Description:
  Cytochrome P4501A1 (CYP1A1) metabolizes polycyclic aromatic hydrocarbons in cigarette smoke to DNA-binding reactive intermediates associated with carcinogenesis. Epidemiologic studies indicate that the majority of coal miners are smokers but have a lower risk of lung cancer than other smokers. We hypothesized that coal dust (CD) exposure modifies pulmonary carcinogenesis by altering CYP1A1 induction. Therefore, male Sprague Dawley rats were intratracheally instilled with 2.5, 10, 20, or 40 mg CD/rat or vehicle (saline); and 11 d later, pulmonary CYP1A1 was induced by intraperitoneal injection of beta-naphthoflavone (BNF; 50 mg/kg). Fourteen days after CD exposure, CYP1A1 protein and activity were measured by Western blot and 7-ethoxyresorufin-O-deethylase activity, respectively. CYP1A1 and the alveolar type II markers, cytokeratins 8/18, were localized and quantified in lung sections by dual immunofluorescence with morphometry. The area of CYP1A1 expression in alveolar septa and alveolar type II cells in response to BNF was reduced by exposure to 20 or 40 mg CD compared with BNF alone. CD exposure significantly inhibited BNF-induced 7-ethoxyresorufin-O-deethylase activity in a dose-responsive manner. By Western blot, induction of CYP1A1 protein by BNF was significantly reduced by 40 mg CD compared with BNF alone. These findings indicate that CD decreases BNF-induced CYP1A1 protein expression and activity in the lung. [Description provided by NIOSH]
• Subjects:
  Carcinogens Coal Coal Mining Dust Epidemiology Hydrocarbons Lung Lung Diseases Mining Neoplasms Occupational Health Polycyclic Aromatic Hydrocarbons Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Smokers Tobacco Products

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• Keywords:
  Alveolar-cells Carcinogenesis Cigarette-smoking Coal-dust Coal-workers Lung-cancer Polycyclic-aromatic-hydrocarbons Pulmonary-system-disorders Respirable-dust Respiratory-system-disorders Risk-factors

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• ISSN:
  1044-1549
• 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:
  171-183
• Volume:
  31
• Issue:
  2
• NIOSHTIC Number:
  nn:20025329
• Citation:
  Am J Respir Cell Mol Biol 2004 Aug; 31(2):171-183
• Contact Point Address:
  Dr. Ann F. Hubbs, Pathology and Physiology Research Branch, Health Effects 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:
  2004
• NORA Priority Area:
  Work Environment and Workforce: Mixed Exposures
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e70e9a89135dc8725c01433c493e84491c1806e59e60f2a6f1adc0ea8f6a9956513173cf0db175f0f6ee671bcede202604309566bd2f2e376009294c0cb46964
• Download URL:
  https://stacks.cdc.gov/view/cdc/196762/cdc_196762_DS1.pdf
• File Type:
  [PDF - 538.06 KB ]