Blood gene expression profiling detects silica exposure and toxicity

Details

• Personal Author:
  Chapman R ; Chen B ; Frazer D ; Joseph P ; Kashon M ; Leonard H ; Li S ; McKinney W ; Richardson D ; Roberts, Jennifer R. ; Sellamuthu R ; Umbright C ; Young S-H
• Description:
  Blood gene expression profiling was investigated as a minimally invasive surrogate approach to detect silica exposure and resulting pulmonary toxicity. Rats were exposed by inhalation to crystalline silica (15 mg/m3, 6 hours/day, 5 days), and pulmonary damage and blood gene expression profiles were determined after latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity as evidenced by histological and biochemical changes in the lungs. The number of significantly differentially expressed genes in the blood, identified by microarray analysis, correlated with the severity of silica-induced pulmonary toxicity. Functional analysis of the differentially expressed genes identified activation of inflammatory response as the major biological signal. Induction of pulmonary inflammation, as suggested by the blood gene expression data, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines observed in the lungs of the silica exposed rats. A gene expression signature developed using the blood gene expression data predicted the exposure of rats to lower, minimally toxic and non-toxic concentrations of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive surrogate approach to detect pulmonary toxicity induced by silica in the rat. However, further research is required to determine the potential application of our findings specifically to monitor human exposure to silica and the resulting pulmonary effects. [Description provided by NIOSH]
• Subjects:
  Biological Factors Blood Cytology Environmental Monitoring Hazardous Substances Irritants Laboratories Lung Lung Diseases Microbiology Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Author Keywords: Silica Biological-effects Biological-factors Cell-biology Cellular-reactions Exposure-assessment Exposure-levels Gene Expression Genotoxic-effects Genotoxicity Inhalation-studies Laboratory-animals Laboratory-testing Lung-cells Lung-disorders Lung-irritants Microscopic-analysis Particle-aerodynamics Particulates Pulmonary-disorders Pulmonary-system-disorders Pulmonary Toxicity Respiratory-hypersensitivity Respiratory-infections Respiratory-irritants Respiratory-system-disorders Statistical-analysis Toxic-effects

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• ISSN:
  1096-6080
• 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:
  253-264
• Volume:
  122
• Issue:
  2
• NIOSHTIC Number:
  nn:20038873
• Citation:
  Toxicol Sci 2011 Aug; 122(2):253-264
• Contact Point Address:
  Pius Joseph, National Institute for Occupational Safety and Health (NIOSH), Toxicology and Molecular Biology Branch, MS 3014, Morgantown, WV 26505
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9a8d51f3f6f15c6006df9978f0df750cf7d897fad6e00150b62b98a42b7e7838610cf18cf2c2f8c80189c0d8199646d1ce6c59f920a06fdf81c5f826cb122405
• Download URL:
  https://stacks.cdc.gov/view/cdc/192416/cdc_192416_DS1.pdf
• File Type:
  [PDF - 302.58 KB ]