Molecular Mechanisms of Pulmonary Response Progression in Crystalline Silica Exposed Rats

Details

• Personal Author:
  Chen BT ; Joseph P ; Kashon M ; Li S ; McKinney W ; Richardson D ; Roberts, Jennifer R. ; Sellamuthu R ; Umbright C ; Young S-H
• Description:
  An understanding of the mechanisms underlying diseases is critical for their prevention. Excessive exposure to crystalline silica is a risk factor for silicosis, a potentially fatal pulmonary disease. Male Fischer 344 rats were exposed by inhalation to crystalline silica (15 mg/m3, six hours/day, five days) and pulmonary response was determined at 44 weeks following termination of silica exposure. Additionally, global gene expression profiling in lungs and BAL cells and bioinformatic analysis of the gene expression data were done to understand the molecular mechanisms underlying the progression of pulmonary response to silica. A significant increase in lactate dehydrogenase activity and albumin content in BAL fluid (BALF) suggested silica-induced pulmonary toxicity in the rats. A significant increase in the number of alveolar macrophages and infiltrating neutrophils in the lungs and elevation in monocyte chemoattractant protein-1 (MCP-1) in BALF suggested the induction of pulmonary inflammation in the silica exposed rats. Histological changes in the lungs included granuloma formation, type II pneumocyte hyperplasia, thickening of alveolar septa and positive response to Masson's trichrome stain. Microarray analysis of global gene expression detected 94 and 225 significantly differentially expressed genes in the lungs and BAL cells, respectively. Bioinformatic analysis of the gene expression data identified significant enrichment of several disease and biological function categories and canonical pathways related to pulmonary toxicity, especially inflammation. Taken together, these data suggested the involvement of chronic inflammation as a mechanism underlying the progression of pulmonary response to exposure of rats to crystalline silica at 44 weeks following termination of exposure. [Description provided by NIOSH]
• Subjects:
  Albumins Animals Environmental Exposure Genetics Laboratories Lung Lung Diseases Morbidity Mortality Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Silicon Dioxide

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• Keywords:
  Albumin Author Keywords: Crystalline Silica Bioinformatics Crystalline Silica Diseases Exposure Levels Fatalities Gene Expression Profile Genes Laboratory Animals Lung Cells Molecular Biology Morbidity Rates Mortality Rates Pulmonary System Pulmonary System Disorders Pulmonary Toxicity Respiratory System Disorders Risk Factors Silica Silicosis Toxicity Mechanisms

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• ISSN:
  0895-8378
• 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:
  53-64
• Volume:
  29
• Issue:
  2
• NIOSHTIC Number:
  nn:20049594
• Citation:
  Inhal Toxicol 2017 Feb; 29(2):53-64
• Contact Point Address:
  Pius Joseph, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health (NIOSH), MS 3014, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Inhalation Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3ae859b4eec2920b0d06935d04f6ec9e758e27657632280906e13d3e7aa03095f84492dda9a5db5c7e41bd5f4cd8601f4405ca21769e9fa4ac8f958a29056470
• Download URL:
  https://stacks.cdc.gov/view/cdc/210299/cdc_210299_DS1.pdf
• File Type:
  [PDF - 1.65 MB ]