TERT-Independent Telomere Elongation and Shelterin Dysregulation After Pulmonary Exposure to Stainless-Steel Welding Fume In-Vivo

Details

• Personal Author:
  Abadin H ; Antonini JM ; Erdely A ; Faroon O ; Kodali VK ; Meighan T ; Shoeb M ; Zarus GM
• 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 afte 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. [Description provided by NIOSH]
• Subjects:
  Chromosomes Occupational Exposure Occupational Health Safety Welding
• Keywords:
  Author Keywords: Welding Fumes Chromosome Damage DNA Damage Genetic Factors In Vivo Study Occupational Exposure Shelterin Complex Telomere Welding Fumes
• ISSN:
  0013-9351
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 3 ; OSHA Region 4 ; 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:
  250
• NIOSHTIC Number:
  nn:20069283
• Citation:
  Environ Res 2024 Jun; 250:118515
• Contact Point Address:
  Mohammad Shoeb, Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry (ATSDR), Centers for Disease Control and Prevention (CDC), 4770 Buford Highway, Mailstop S106-5, Chamblee, GA, 30341
• Email:
  ywo7@cdc.gov
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Environmental Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dd0aedecdd53d94c4b108de59ad1cd21295c79a15de7cd08f68e2281ff7c94a4e746e186f084e0ea4fdd4dab40d4982022a59c2f7285951f626c8ae38e6c5333
• Download URL:
  https://stacks.cdc.gov/view/cdc/207787/cdc_207787_DS1.pdf
• File Type:
  [PDF - 870.24 KB ]