Toluene Dose-Response and Preliminary Study of Proteomics for Neuronal Cell Lines

Abstract

Toluene, a jet fuel component, is a potential contaminant in aircraft. Effects of toluene exposure include headache or fatigue. The objective of this study was to perform a preliminary investigation of the cellular and molecular effects of toluene on murine cell lines including Cath.a, C8-B4, CLU199, and HT22. The study tests two methods: direct dosing of toluene in the media and vapor exposure in glass chambers. To better define the complex signaling response to toluene, the two exposure models are characterized by cell viability assays and Tandem Mass Tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS) quantitative proteomics proteome pathway analysis. Cell viability in response to direct dosing in a vehicle demonstrated a dose-dependent decrease in cell viability for all cell lines. Cytoscape 3.1.0 Reactome FI pathway analysis of Cath.a cells following direct dosing with 0.2 and 2 mM toluene revealed a dose-dependent toxicity increase of modulated protein nodes related to oxidative stress such as energy reserve metabolism, cell-death signaling, cytoskeletal rearrangement, DNA damage response, targeted protein degradation and apoptosis. While cell viability testing of all four cell lines exposed to 200 ppm toluene vapor for 1hour did not result in any detectable decrease of cell viability, proteomic analysis displayed minor signs of cellular stress with a majority of modulated proteins. These findings contribute to understanding the complex protein modifications within normally conserved proteins and toluene induced activation of cellular signaling pathways, which will aid in determining initiating mechanisms of brain toxicity from low level doses.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2015
Accession Number
ADA627076

Entities

People

  • David A. Dixon
  • David R. Mattie
  • John J. Schlager
  • Kyung O. Yu
  • Laura K. Braydich-stolle
  • Michael J. Ray
  • Mitchell L. Meade
  • R. A. James
  • Renell H. Capati
  • Teresa R Sterner

Organizations

  • Air Force Research Laboratory

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Air Force Research Laboratories
  • Amino Acids
  • Apoptosis
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Central Nervous System
  • Chemistry
  • Culture Techniques
  • Liquid Chromatography
  • Mass Spectrometry
  • Metabolism
  • Nervous System
  • Peptides
  • Proteins
  • Proteomics
  • Spectrometry

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Genetics
  • Organic Chemistry

Technology Areas

  • Biotechnology