Effects of Diesel Exhaust Particles (DEP) Exposure on Pulmonary Cytochrome P-450 (P-450) Metabolism

Details

• Personal Author:
  Barger MW ; Castranova, Vincent ; Kane E ; Ma JYC
• Description:
  Polycyclic aromatic hydrocarbons (PAHs) associated with DEP require bioactivation by P-450 to exert their toxic/carcinogenic effects. The objective of the present study was to determine the effects of exposure of rats to DEP on pulmonary P-450 metabolism. Rats were dosed with a single intratracheal instillation of either 5 or 35 mg/kg of DEP or carbon black (CB). CB was used as a particle control without absorbed organics. Rats were sacrificed 3 days after exposure, and pulmonary microsomes were isolated by differential centrifugation of lung homogenates. The protein level and activity of P-450 isozymes, CYP1A1 and CYP2B1, were monitored to assess the effects of DEP exposure on the P-450 enzyme system. CYP2B1 and CYP1A1 activities were measured by the Odealkylation of 7-pentoxyresorufin and 7-ethoxyresorufin, respectively. The protein levels were determined by Western blot analysis. At both exposure doses, DEP or CB significantly reduced CYP2B1 activity, while only high dose exposure lowered CYP2B1 protein level. At 5 mg/kg of DEP or CB, CYP1A1 activity was significantly lowered without affecting the protein level. At the 35 mg/kg exposure level, DEP significantly increased CYP1A1 activity and protein level, whereas CB reduced CP1A1 activity and had little effect on the protein level. These data suggest that the effects of DEP on pulmonary P-450 are two fold: an induction of CYP1A1 by PAHs, the organic components of DEP, and a reduction of CYP2B1 activity due for the most part to the carbonaceous core of the particles. Both effects may play important roles in DEP induced toxicity. [Description provided by NIOSH]
• Subjects:
  Animals Carcinogens Energy Metabolism Environmental Exposure Hydrocarbons Laboratories Lung Lung Diseases Occupational Health Polycyclic Aromatic Hydrocarbons Respiratory System Respiratory Tract Diseases Safety Vehicle Emissions

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• Keywords:
  Animal Studies Carcinogenesis Carcinogenicity Diesel Exhausts Exposure Assessment Exposure Levels Laboratory Animals Metabolism Polycyclic Aromatic Hydrocarbons Pulmonary System Pulmonary System Disorders Respiratory System Disorders Toxic Effects

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• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  163
• Issue:
  5
• NIOSHTIC Number:
  nn:20021374
• Citation:
  Am J Respir Crit Care Med 2001 Apr; 163(5)(2)(Suppl):A172
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Part Number:
  2
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine. Abstracts of the American Thoracic Society 2001 International Conference, May 18-23, 2001, San Francisco, California
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f2b73e2c2b240d08de0cb7b38f69a1186a9b60672d19170700c640db0fcfa1757175936797ac9cc35d7ffaf23edb9d35ae8e3a5365a45325fd9a6330748efc6c
• Download URL:
  https://stacks.cdc.gov/view/cdc/198725/cdc_198725_DS1.pdf
• File Type:
  [PDF - 139.53 KB ]