Peripheral blood gene expression profiling reveals silica-induced pulmonary toxicity

Details

• Personal Author:
  Chapman R ; Chen B ; Frazer D ; Joseph P ; Kashon M ; Leonard D ; Li S ; McKinney W ; Richardson D ; Roberts J ; Sellamuthu R ; Umbright C ; Young S
• Description:
  The present research aimed to investigate peripheral blood gene expression profiling as a minimally invasive surrogate approach to study silica-induced pulmonary toxicity. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days). Pulmonary damage and blood gene expression profiles were determined at various latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity in the rats as evidenced by histological changes in the lungs and elevation of LDH activity in the bronchoalveolar lavage fluid (BALF). Analysis of global gene expression profiles in the blood of the rats identified genes that were differentially expressed in response to silica exposure. The differential blood gene expression profiles correlated with the pulmonary toxicity parameters in the silica exposed rats. Genes involved in biological functions such as inflammatory response, cancer, pulmonary damage, oxidative stress, energy metabolism, fibrosis, etc, were found differentially expressed in the blood of the silica exposed rats compared with the controls. Induction of pulmonary inflammation in the silica exposed rats, as suggested by differential expression of inflammatory response genes in the blood, was supported by significant increases in the number of neutrophils and macrophages as well as the activity of pro-inflammatory chemokines - MCP1 and MIP2, observed in the BALF of the silica exposed rats. A silica-responsive blood gene expression signature developed using the gene expression data predicted with significant accuracy the exposure of rats to lower concentrations (1 and 2 mg/m3) of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as an efficient surrogate approach to study silica-induced pulmonary toxicity. Disclaimer: The findings and conclusions in this abstract have not been formally disseminated by NIOSH and should not be constructed to represent any agency determination or policy. [Description provided by NIOSH]
• Subjects:
  Animals Cytology Hazardous Substances Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Animal-studies Biological-effects Cell-biology Laboratory-animals Laboratory-testing Lung-cells Lung-disorders Molecular-biology Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Quantitative-analysis Respiratory-infections Respiratory-system-disorders Statistical-analysis Toxic-effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; 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:
  120
• NIOSHTIC Number:
  nn:20038628
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):498
• CAS Registry Number:
  Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:71b55e2669ae62810489f21816c5bc62bc2eae2a0d183222e602d00159e2429eb5c8e66ac76e130ae88be86566b3d500e4885711d0e8290d016ddf1f115596bc
• Download URL:
  https://stacks.cdc.gov/view/cdc/192274/cdc_192274_DS1.pdf
• File Type:
  [PDF - 1.10 MB ]