Pulmonary toxicity and global gene expression changes in response to subchronic inhalation exposure to crystalline silica in rats

Details

• Personal Author:
  Chen BT ; Frazer DG ; Gu J ; Joseph P ; Kashon ML ; McKinney W ; Richardson D ; Roberts, Jennifer R. ; Sellamuthu R ; Umbright C ; Young S
• Description:
  Exposure to crystalline silica results in serious health effects, most notably, silicosis and cancer. An understanding of the mechanism(s) underlying the silica-induced pulmonary toxicity is critical for the intervention and/or prevention of adverse health effects. Rats were exposed by inhalation to silica at a concentration of 15 mg/ m3, 6 hours/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression changes were determined in the lungs of the control (air) and silica exposed rats at the end of each exposure period. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase activity and accumulation of alveolar macrophages and infiltrating neutrophils in the bronchoalveolar lavage fluid, was seen in the rats depending on the silica exposure duration. The most severe histological changes, seen in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. In addition, silica was visible in the lungs of the rats belonging to the 12-week exposure group. A significant increase in the number of neutrophils seen in the blood indicated silica-induced systemic inflammation in the rats. Microarray analysis of the global gene expression profiles of the lungs detected significant differential expression (FDR p <0.05 and fold change >1.5) of 38, 77 and 99 genes in the rats exposed to silica for 3-, 6- and 12-weeks, respectively, compared to the time-matched controls. Bioinformatics analysis of the differentially expressed genes identified significant enrichment of functions, networks and pathways related to inflammation, cancer, oxidative stress, fibrosis and tissue remodeling in the lungs of the silica exposed rats. Collectively, the results of our study provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic exposure to crystalline silica in rats. [Description provided by NIOSH]
• Subjects:
  Animals Blood Genetics Hazardous Substances Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Analytical-processes Blood-cells Cancer Exposure-levels Genes Health-hazards Laboratory-animals Lung-cells Lung-disorders Lung-fibrosis Lung-tissue Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-system-disorders Silica-dusts Silicosis Toxic-effects Toxins

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• ISSN:
  1096-6080
• 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:
  138
• Issue:
  1
• NIOSHTIC Number:
  nn:20043933
• Citation:
  Toxicologist 2014 Mar; 138(1):450
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85d71c8ecf985fa7b2d2c5bff92d5c3f44e08db5517f93df4c628c6f74617a37e9fda1dab70531b86451b09f12d5f1308eebbc565cb52c3883a82fed98c04aac
• Download URL:
  https://stacks.cdc.gov/view/cdc/199800/cdc_199800_DS1.pdf
• File Type:
  [PDF - 250.48 KB ]