Serum Peptidome: Diagnostic Window into Pathogenic Processes Following Occupational Exposure to Carbon Nanomaterials

Details

• Personal Author:
  Campen MJ ; Dahm, Matthew M. ; Erdely A ; Eye T ; Mostovenko E ; Ottens AK ; Schubauer-Berigan, Mary K. ; Young TL
• Description:
  Background: Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up. Methods: Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance. Results: In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. Conclusions: The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Diagnosis Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Author Keywords: Carbon Nanotubes Blood Serum Carbon Nanofbers Carbon Nanofibers Carbon Nanotubes Cardiovascular CNF CNT Diagnostic Techniques Health Outcomes Inhalation Mass Spectrometry Nanomaterials Nanotoxicology Occupational Peptidomics Thrombosis

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• ISSN:
  1743-8977
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New Mexico ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 6 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DFSE - Division of Field Studies and Engineering ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  39
• Volume:
  18
• NIOSHTIC Number:
  nn:20063911
• Citation:
  Part Fibre Toxicol 2021 Oct; 18:39
• Contact Point Address:
  Andrew K. Ottens, Department of Anatomy and Neurobiology, Virginia Commonwealth University, PO Box 980709, Richmond, VA 23298, USA
• Email:
  akottens@vcu.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  True
• Start Date:
  20150930
• Source Full Name:
  Particle and Fibre Toxicology
• End Date:
  20190929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f722668b283898503d1d89bc40dafe774cef4f3776970310f9a9655bd13001b78a65212828aa5bd6b6b91921c6a47480ac791d0156b2f0c2381379ff300403eb
• Download URL:
  https://stacks.cdc.gov/view/cdc/222449/cdc_222449_DS1.pdf
• File Type:
  [PDF - 3.96 MB ]