Apoptosis Induction After Silica Inhalation in Rats

Details

• Personal Author:
  Castranova, Vincent ; Khan A ; McLaurin JL ; Mercer R ; Millecchia L ; Porter DW ; Ramsey D ; Suarez F ; Teass A
• Description:
  Occupational exposure to crystalline silica (quartz) has been associated with lung damage and fibrosis. In vitro studies have shown that silica induces apoptosis in human alveolar macrophages and in vivo after intratracheal instillation in rats. These studies suggested that silica inhalation may stimulate apoptosis and that apoptosis may play a role in the silicotic process. A first step in investigating these questions would be to establish the temporal relationship between silica exposure, apoptosis and lung inflammation and damage. Thus, rats were exposed to filtered air (control) or silica aerosol of 15 mg/m3 (6 hr/day, 5 days/week) and apoptosis in bronchoalveolar lavage cells (BALC) or lung tissue were determined during a 116 day exposure. The lung inflammatory response to inhaled silica was monitored by determining polymorphonuclear leukocyte and alveolar macrophages (AM) in BALC while lung damage was assessed by measuring acellular bronchoalveolar lavage fluid albumin. In silica-exposed rats, all three parameters were elevated versus controls from 5-41 days of exposure, then dramatically increased thereafter versus controls. Apoptosis in BALC was measured with a commercial ELISA assay kit, and values from silica-exposed rats were normalized to controls. The BALC data indicate that apoptosis was evident after only 5 days of exposure, increased steadily until 20 days of exposure, remained relatively constant through 79 days of exposure and then decreased. Lungs, removed from both control and silica-exposed rats, were fixed with 10% neutral buffered formalin and embedded in paraffin for further examination. Apoptosis was assessed in lung tissue slices using the TdT-mediated dUTP biotin nick end-labeling (TUNEL) assay. The TUNEL assay results were consistent with the observed trends in apoptosis measured in BALC and also indicated that the apoptotic cells were AM. These data indicate that the inhalation of silica stimulates apoptosis as predicted, and the magnitude of the apoptotic response changed during the silica exposure. Finally, the observed acceleration of lung inflammation and damage was associated with a decline in apoptosis, suggesting that apoptosis may playa role in the silicotic process. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Aluminum Silicates Animals Chemistry Chemistry, Analytic Dust Environmental Monitoring Hazardous Substances Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Airborne-dusts Airborne-fibers Airborne-particles Analytical-chemistry Analytical-methods Animal-studies Dust-exposure Dust-inhalation Dust-particles Exposure-assessment Laboratory-animals Particulate-dust Particulates Pulmonary-disorders Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Silica-dusts Silicates Statistical-analysis Toxic-materials Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  131-132
• Volume:
  48
• NIOSHTIC Number:
  nn:20027968
• Citation:
  Toxicologist 1999 Mar; 48(1-S):131-132
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:09a09b0528ae8271910ffda9fe0db8839714631a1d73c44dbe56edba9e378b2a0be704ba30463399cac90eeaf578acd4996e36c1bc13a9601fae9a88fa65c873
• Download URL:
  https://stacks.cdc.gov/view/cdc/189704/cdc_189704_DS1.pdf
• File Type:
  [PDF - 229.22 KB ]