Cigarette Smoke Exposure Exacerbated Silica-Induced Pulmonary Toxicity

Details

• Personal Author:
  Joseph P ; Kashon M ; McKinney W ; Mustafa G ; Sager T ; Umbright C
• Description:
  Smoking, an avoidable life style factor, may modify the lung response to silica exposure including cancer and silicosis. Studies have shown that smoking induces oxidative stress and inflammation, etiological factors involved in the development and progression of cancer and silicosis. Nevertheless, the precise role of cigarette smoke (CS) exposure on the lung response to silica exposure and the underlying mechanisms are unclear. Therefore, the objectives of the present study were to determine the role of CS on lung response to silica exposure and the underlying mechanism. Male Fischer 344 rats were exposed by inhalation to air, crystalline silica (15 mg/m3, 6 hrs/day, 5 days), CS (80 mg/m3, 3 hrs/day, twice weekly, 6 months), or silica (15 mg/m3, 6 hrs/day, 5 days) followed by CS (80 mg/m3, 3 hrs/day, twice weekly, 6 months). The rats were euthanized 6 months following initiation of the exposures and lung response parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts, and cytokines in broncho-alveolar lavage (BAL) were assessed. Silica exposure resulted in significant lung toxicity as evidenced by lung histological changes, enhanced neutrophil infiltration, increased LDH levels, enhanced oxidant production, and increased cytokine levels. The CS exposure had only a minimal effect on the toxicity parameters. However, the combined exposure to silica and CS caused a significant increase in lung response, compared to silica or CS exposure alone. For example, CS or silica exposure alone resulted in neutrophil infiltration 5 and 150 times, respectively, compared to the air-exposed controls. The combined exposure to silica plus CS, on the other hand, caused a neutrophil infiltration that was 500 times higher compared to air controls suggesting a synergistic effect of silica and CS on lung toxicity. Global gene expression changes detected in the rat lungs correlated with the toxicity. Bioinformatic analysis of the gene expression data demonstrated significant enrichment in functions and pathways relevant to silica exposure which correlated with the lung toxicity. Unique pathways relevant to lung response to silica exposure, for example disruption of circadian rhythm signaling, were detected in the rat lungs exposed to silica and CS. Collectively our data demonstrated an exacerbation of silica-induced lung toxicity by CS exposure and the molecular mechanisms underlying the exacerbated toxicity. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Histology Immune System Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Smokers Tobacco Products Toxicology

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• Keywords:
  Bioinformatics Cancer Cell Signaling Cigarette Smoking Cytokines Dose Response Exposure Assessment Exposure Levels Gene Expression Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Disorders Lung Tissue Molecular Signaling Neutrophils Oxidative Stress Pulmonary Effects Silica Silicosis Smoking Synergistic Effects Toxic Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20059003
• Citation:
  Toxicologist 2020 Mar; 174(1):521
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1e483084659ebc0d8e4f56ef246089be589998866a16ce62a002a28571dd59a2ee0e1f338182c848915b603674c8589ec46da4215d99bf00816a61cf7e1eed84
• Download URL:
  https://stacks.cdc.gov/view/cdc/223342/cdc_223342_DS1.pdf
• File Type:
  [PDF - 523.31 KB ]