Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

Details

• Personal Author:
  Joseph P ; Kashon M ; Li S ; Sellamuthu R ; Umbright C
• Description:
  A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. [Description provided by NIOSH]
• Subjects:
  Hazardous Substances Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Author Keywords: Crystalline Silica Autoimmunity Biological-effects Cancer Cell-function Cell-growth Cell-migration Cellular-reactions Cellular-structures Exposure-methods Gene-mutation Gene Expression Profile Genotoxic-effects Inhalation-studies Laboratory-animals Laboratory-testing Lung-disease Lung-disorders Lung-function Mechanisms Molecular-structure Pulmonary-disorders Pulmonary-system-disorders Pulmonary Toxicity Respiratory-system-disorders Silica-dusts Silicosis Toxic-effects Toxic-materials

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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
• Volume:
  23
• Issue:
  14
• NIOSHTIC Number:
  nn:20040051
• Citation:
  Inhal Toxicol 2011 Dec; 23(14):927-937
• Contact Point Address:
  Pius Joseph, MS 3014, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2012
• 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-512:6f6553bdac3be33246edc3ff933f5ac260fe5ed6c4706a97cb47f358bc8a56f3332f58d4b8876b4e14c29af07e3671f0c380961c95a2ac1b080bb5cd18bc7d90
• Download URL:
  https://stacks.cdc.gov/view/cdc/193045/cdc_193045_DS1.pdf
• File Type:
  [PDF - 761.45 KB ]