Pulmonary Toxicity and Global Gene Expression Changes in Response to Sub-Chronic Inhalation Exposure to Crystalline Silica in Rats

Details

• Personal Author:
  Chen B ; Gu JK ; Joseph P ; Kashon M ; McKinney W ; Richardson D ; Roberts, Jennifer R. ; Schwegler-Berry D ; Sellamuthu R ; Umbright C ; Young S-H
• Description:
  Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m3, 6 hr/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression profiles were determined in lungs at the end of each exposure period. Crystalline silica was visible in lungs of rats especially in the 12-week group. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase (LDH) activity and albumin content and accumulation of macrophages and neutrophils in the bronchoalveolar lavage (BAL), was seen in animals depending upon silica exposure duration. The most severe histological changes, noted in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. Microarray analysis of lung gene expression profiles detected significant differential expression of 38, 77, and 99 genes in rats exposed to silica for 3-, 6-, or 12-weeks, respectively, compared to time-matched controls. Among the significantly differentially expressed genes (SDEG), 32 genes were common in all exposure groups. Bioinformatics analysis of the SDEG identified enrichment of functions, networks and canonical pathways related to inflammation, cancer, oxidative stress, fibrosis, and tissue remodeling in response to silica exposure. Collectively, these results provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic inhalation 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 Author Keywords: Crystalline Silica Blood-cells Cancer Crystalline Silica Exposure-levels Gene Expression Genes Health-hazards Health Effects Inhalation Exposure Laboratory-animals Lung-cells Lung-disorders Lung-fibrosis Lung-tissue Mechanisms Pulmonary-function Pulmonary-system Pulmonary-system-disorders Pulmonary Toxicity Respiration Respiratory-system-disorders Silica-dusts Silicosis Toxic-effects Toxins

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• ISSN:
  1528-7394
• 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:
  80
• Issue:
  23
• NIOSHTIC Number:
  nn:20050662
• Citation:
  J Toxicol Environ Health A 2017 Nov; 80(23-24):1349-1368
• 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
• Email:
  pcj5@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a7a75e8c3f712f8be4e3170864b38da543131445ee4d7f0ab848c8b9fa2a70ef4280e05a1de01793bb7c82fdd38a3cc09cccdd08aa797351b9dfd8d8161a7ea0
• Download URL:
  https://stacks.cdc.gov/view/cdc/210915/cdc_210915_DS1.pdf
• File Type:
  [PDF - 2.21 MB ]