Silica inhalation-altered expression of telomere maintenance genes in lung tissue of rats

Details

• Personal Author:
  Antonini JM ; Erdely A ; Joseph P ; Kodali V ; Roberts, Jennifer R. ; Shoeb M ; Umbright C
• Description:
  Occupational exposure to silica causes severe health effects, such as pulmonary fibrosis and lung carcinoma. Identification of molecular targets and mechanisms of silica-induced pulmonary toxicity is important for intervention and prevention of lung disease. Telomeres consist of tandem repeats of TTAGGG DNA sequences and are located at the end of chromosomes, preventing chromosomal fusion and degradation. Telomeres shorten with cell division leading to genomic instability and cellular senescence. Shelterin (e.g., POT1) and other proteins (e.g., TTI2, RTEL1) involved in telomere maintenance play an important role in maintaining telomere length and integrity. The goal was to assess the effect of silica exposure on the regulation of different genes involved in telomere maintenance in an animal model. Male Fischer 344 rats were exposed by inhalation to silica using two regimens: (1) 15 mg/m3 for 6 hr/d x 3, 6, and 12 wk, assessed 1 d post-exposure; (2) 15 mg/m3 for 6 hr/d x 1 wk, assessed 44 wk post-exposure. After exposure, portions of right lungs were homogenized, total RNA was isolated, cDNA was obtained, and expression of telomere maintenance genes was assessed. At all time points post-exposure, mRNA expression of POT1, RTEL1, and TTTI2 was significantly decreased in lung tissue of silica-exposed animals compared to air controls. Reduced expression of these genes causes disruption of assembly of the telomere and induces DNA damage. Analysis of a focused array for genes associated with telomere function and regulation indicated a reduced expression (p<0.01) of 49 genes after 3 wk post-exposure. However, by 44 wk after a 1 wk exposure, 10 of these genes were overexpressed, whereas 29 of these genes remained downregulated. Array findings indicated acute and subchronic effects on telomere- associated genes after silica exposure. This study indicates that measurement of genes involved in telomere maintenance may serve as a potential biomarker related to silica exposure and also may offer insight into the mechanism of silica-induced lung disease and tumorigeneses. [Description provided by NIOSH]
• Subjects:
  Biomarkers Carcinogens Cell Division Chromosomes Environmental Exposure Genetics Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Analytical Models Cell Division Cellular Function Chromosome Damage Crystalline Silica Deoxyribonucleic Acids DNA DNA Damage DNA Microarrays Exposure Assessment Exposure Levels Gene Expression Gene Regulation Genes Inhalation Inhalation Studies Laboratory Animals Laboratory Testing Lung Cells Lung Disease Lung Tissue Proteins Pulmonary System Ribonucleic Acids RNA Silica Silica Dusts Tumorigenesis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; 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:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049455
• Citation:
  Toxicologist 2017 Mar; 156(1):325
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5f2a74e09d87442f63e54e71fa41e5f94c40dd65d7083f8da9c3a03e9650396217bbe44c2a86f9a054e32eb3cd5915a64a4e04d211354e2787818800307fdf90
• Download URL:
  https://stacks.cdc.gov/view/cdc/203899/cdc_203899_DS1.pdf
• File Type:
  [PDF - 944.39 KB ]