Functional Significance of the SLC26A4 Gene in Silica-Induced Pulmonary Toxicity

Details

• Personal Author:
  Sager T
• Description:
  Occupational exposure to silica may result in potentially fatal diseases such as silicosis and cancer. Understanding molecular mechanisms responsible for silica-induced pulmonary toxicity is of great importance in preventing silicosis and other effects associated with occupational silica exposure. Previous studies in our laboratory identified a correlation between silica-induced pulmonary toxicity and SLC26A4 gene overexpression in the lungs of rats. However, the functional significance of this gene in silica induced pulmonary toxicity is not understood. To determine the role of the SLC26A4 gene in silica-induced pulmonary toxicity, SLC26A4 wild type (WT) and knockout (KO) mice were employed. All mice were exposed to either air or crystalline silica (15 mg/m3, 6 hours/day, 4 days) and pulmonary toxicity was assessed at 1 day, 3 months, 6 months, and 9 months post-exposure. Pulmonary response parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts (including infiltrating neutrophils and alveolar macrophages), and gene expression changes were assessed. Silica exposure resulted in the induction of pulmonary toxicity and inflammation in both the WT and KO mouse strains, compared to corresponding air exposed controls. However, there were significant differences (p<0.05) in the measured pulmonary toxicity parameters between silica exposed WT and KO groups. For example, induction of pulmonary inflammation in the silica exposed mice was hallmarked by a significant increase in infiltration of neutrophils in the lung. This infiltration was vastly different between the WT and KO groups. Specifically, at 3 months post-exposure neutrophil infiltration in the WT mice was 480 fold higher compared to air exposed controls while being 205 fold higher in the KO mice. At 6 months post-exposure, neutrophil infiltration in the WT mice was 192 times higher than air controls while the KO mice had, a significantly lower, 54 fold increase in PMN number, compared to air controls. At 9 months post-exposure neutrophil number was 45 fold higher in WT mice and only 9 fold higher in KO mice compared to air controls. In conclusion, both the WT and KO mice presented with an enhancement in pulmonary toxicity parameters measured, however, the severity of silica induced pulmonary toxicity was more in the WT mice compared to the KO mice. These findings support the hypothesis that the SLC26A4 gene does, in fact, play a role in silica induced pulmonary toxicity. [Description provided by NIOSH]
• Subjects:
  Blood Environmental Exposure Genetics Immune System Laboratories Lung Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Crystalline Silica Dose Response Exposure Assessment Exposure Levels Gene Expression Genes Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Cells Neutrophils Pulmonary Effects Pulmonary System Disorders Silica Toxic Effects

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• ISSN:
  1096-6080
• 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
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20054964
• Citation:
  Toxicologist 2019 Mar; 168(1):240
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ded6e83d1c5a246fa050a4054cdcbd9ef600b680c42bcdbbe2e50ab71c1c7b7685066686b287ee12c3e5450fd81b1f08719f8e2b205eba08c3da0603780fb089
• Download URL:
  https://stacks.cdc.gov/view/cdc/217370/cdc_217370_DS1.pdf
• File Type:
  [PDF - 860.30 KB ]