Assessment of Welding Fume Exposure on Telomere Length and Regulation in Peripheral Blood Mononuclear Cells and Lung Tissue in Rats

Details

• Personal Author:
  Antonini J ; Boyce G ; Erdely A ; Kodali V ; Meighan T ; Roach K ; Roberts J ; Shoeb M ; Xin X
• Description:
  Telomeres are DNA fragments at the ends of chromosomes that protect genetic information during cell proliferation. Telomeres control DNA damage response (DDR) and DNA repair activity during cell division by regulating ATM and ATR kinases. Protection of telomeres 1 (POT1) protein specifically binds the 3' overhang of the telomere and plays a key role in chromosomal end protection and telomere length regulation. In this study, we examined POT1 mRNA expression and telomere length and regulation by shelterin complex proteins in peripheral blood mononuclear cells (PBMCs) and non-lavaged whole lung tissue in male Sprague-Dawley rats following exposure, by intratracheal instillation, to 2 mg/rat of manual metal arc-stainless steel welding fume (WF) particulate or saline (vehicle control). PBMCs and lung tissue were harvested at 30 d after instillation. WF is a complex mixture of metals (41% Fe, 28% Cr, 17% Mn, 3% Ni) with a count mean diameter of 600 nm. The PBMCs recovered from WF-exposed animals had increased telomere length as analyzed by fluorescent in situ hybridization (FISH), flow cytometry, and qPCR compared to controls. Altered expression of shelterin regulatory proteins, tripeptidyl-peptidase 1 (TPP1) and TERF1-interacting nuclear factor 2 (Tin2), was observed in PBMCs and lung tissues. Also, increased telomere length in lung tissue as analyzed by qPCR was observed in the WF group compared to control. However, qPCR analysis showed that POT1 expression levels in the lung tissue of the WF group relative to those in the control group (T/N ratio) was significantly lower, leading to the activation of ATR expression that was not observed in PBMCs. These results indicate that exposure to WF down-regulated lungs POT1 which in turn activated ATR-dependent DNA damage signaling and telomere elongation in the lungs, as well as activation of telomerase-independent pathway, an alternative mechanism leading to telomere elongation in PBMCs. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Blood Cell Division Cells, Cultured Chromosomes Environmental Exposure Hazardous Substances Laboratories Lung Metals Nucleotides Occupational Health Respiratory System Safety Toxicology Welding

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• Keywords:
  Arc Welding Blood Cells Cell Cultures Cell Culture Techniques Cell Division Cell Proliferation Cellular Effects Chromosome Damage Deoxyribonucleic Acids DNA DNA Damage Exposure Assessment Exposure Levels Laboratory Animals Laboratory Testing Lung Tissue Proteins Ribonucleic Acids RNA Signaling Pathways Stainless Steel Toxic Fumes Welding Fumes

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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:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20054913
• Citation:
  Toxicologist 2019 Mar; 168(1):112
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3) ; Iron (CAS RN 7439-89-6) ; Manganese (CAS RN 7439-96-5) ; Nickel (CAS RN 7440-02-0) ; Stainless Steel (CAS RN 12597-68-1)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e2dbd8dbf5e4ce3118735410ff8acaf48bcbd2da7fce8ca576fbd0862b05837dc24b0a8289b09327f6e633af9e6b348d8eaf1c64aae0f02597e01bfa59ef700b
• Download URL:
  https://stacks.cdc.gov/view/cdc/217323/cdc_217323_DS1.pdf
• File Type:
  [PDF - 866.90 KB ]