TERT-independent telomere elongation and shelterin dysregulation after pulmonary exposure to stainless-steel welding fume in-vivo

Details

• Alternative Title:
  Environ Res
• Personal Author:
  Shoeb, Mohammad ; Meighan, Terence ; Kodali, Vamsi K. ; Abadin, Henry ; Faroon, Obaid ; Zarus, Gregory M. ; Erdely, Aaron ; Antonini, James M.
• Description:
  Telomeres are inert DNA sequences (TTAGGG) at the end of chromosomes that protect genetic information and maintain DNA integrity. Emerging evidence has demonstrated that telomere alteration can be closely related to occupational exposure and the development of various disease conditions, including cancer. However, the functions and underlying molecular mechanisms of telomere alteration and shelterin dysregulation after welding fume exposures have not been broadly defined. In this study, we analyzed telomere length and shelterin complex proteins in peripheral blood mononuclear cells (PBMCs) and in lung tissue recovered from male Sprague-Dawley rats following exposure by intratracheal instillation (ITI) to 2 mg/rat of manual metal arc-stainless steel (MMA-SS) welding fume particulate or saline (vehicle control). PBMCs and lung tissue were harvested at 30 d after instillation. Our study identified telomere elongation and shelterin dysregulation in PBMCs and lung tissue after welding fume exposure. Mechanistically, telomere elongation was independent of telomerase reverse transcriptase (TERT) activation. Collectively, our findings demonstrated that welding fume-induced telomere elongation was (a) TERT-independent and (b) associated with shelterin complex dysregulation. It is possible that an alteration of telomere length and its regulatory proteins may be utilized as predictive biomarkers for various disease conditions after welding fume exposure. This needs further investigation.
• Subjects:
  Air Pollutants, Occupational Animals Inhalation Exposure Leukocytes, Mononuclear Lung Male Rats Rats, Sprague-Dawley Stainless Steel Telomerase Telomere Telomere-Binding Proteins Welding

  More +
• Keywords:
  DNA Damage Shelterin Complex Welding Fumes
• Source:
  Environ Res. 250:118515
• Pubmed ID:
  38373547
• Pubmed Central ID:
  PMC11375608
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  250
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0dccea020d582476dca4bbeef69b17b4472e9632c46e3eee6ed5c957f015fbcd642f59e761f964614d1f677620cb2c94f3a203803b2285e0edfd21fccbaa893d
• Download URL:
  https://stacks.cdc.gov/view/cdc/162367/cdc_162367_DS1.pdf
• File Type:
  [PDF - 798.13 KB ]