Mass spectrometry development of occupational nanomaterial exposure biomarkers

Details

• Personal Author:
  Campen MJ ; Erdely A ; Mostovenko E ; Muldoon PP ; Ottens AK ; Vucetic A
• Description:
  Recent growth in application of engineered nanomaterials (ENMs) causes increased human occupational exposure creating a demand for health risk assessment and regulatory guidelines. Studies are needed to understand the breadth of ENM's toxic potential and biological effects on humans. For this purpose, novel biomarkers are needed for efficient and accurate safety profiling of ENM exposure. Here we present an approach to discover biofluid-based signatures of nanomaterial exposure relevant to mechanisms of systemic toxicity. Male C57BL/6 mice were exposed to 10 or 40 microg of multi-walled carbon nanotubes (MWCNT-7, 49 nm mean diameter and 3.86 microm mean length) or vehicle (0.6 mg/ml mouse albumin and 0.01 mg/ml 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) by oropharyngeal aspiration with serum, cerebrospinal, and bronchial lavage fluids collected 4 h post-exposure. A sub 10 kDa molecular fraction was extracted under denaturing conditions. Data were acquired using unbiased data-independent mass spectrometry (MS). Statistically significant and measures were processed in ProteinLynx Global Server and sequenced using in-house software EndogeSeq against selective subsets of a mouse UniProt protein database. MS results provided reproducible quantification within biofluids. For example, 9000 serum factors were quantified across exposure groups in serum alone, with 307 and 250 MWCNT-responsive measures identified at the 10 and 40 microg doses, respectively. Results reveal a combination of dose-dependent and -independent factors, comprising distinctive signatures of increasing and decreased measures. Furthermore, identified peptides point to proteolytic processing by metalloproteinases with products localized within and outside of signaling domains. Produced peptides such as that for CUB and sushi domain-containing protein 1 and interferon regulatory factor 1 further originate from regulatory domains involved in inflammatory modulation, suggesting bioactive potential. Overall, findings demonstrate the complex biomolecular response to ENM exposure and its potential in developing mechanistically-relevant occupational safety biomarker assays. [Description provided by NIOSH]
• Subjects:
  Albumins Biological Assay Biomarkers Body Fluids Environmental Exposure Immune System Laboratories Occupational Health Safety Software Toxicology

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• Keywords:
  Albumin Analytical Instruments Bioactivation Bioassays Body Fluids Carbon Nanotubes Cell Signaling Cerebrospinal Fluid Computer Software Dose Response Exposure Assessment Exposure Levels Immune Reaction Laboratory Animals Laboratory Testing Mass Spectrometry Metalloproteins Molecular Signaling Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Nanotubes Peptides Proteins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; New Mexico ; OSHA Region 3 ; OSHA Region 6 ; Virginia ; 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:20049427
• Citation:
  Toxicologist 2017 Mar; 156(1):215
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center, Albuquerque, New Mexico
• Peer Reviewed:
  False
• Start Date:
  20150930
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• End Date:
  20190929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:26ca8315a8b180ecba1be0c5c9c114a357553a0d363e709e5c1da56fccfc459d1bc5aa98880ad944f1946fae62a48f368d30118b333e07f00e67be9654099f63
• Download URL:
  https://stacks.cdc.gov/view/cdc/203874/cdc_203874_DS1.pdf
• File Type:
  [PDF - 949.88 KB ]