Ricin Toxicity in BALB/C 3T3 Cells: Peptide Biomarkers of Exposure
Abstract
This report is required for the U.S. Army Edgewood Chemical Biological Center In-House Laboratory Independent Research project, "Cell Toxicity by NMR and Mass Spectrometry." Nuclear magnetic resonance and/or mass spectrometry (MS) in combination with chemometrics analysis can yield physiological details in the form of metabolome or proteome biomarker information. We have analyzed trypsinized cellular protein extracts from BALB/c 3T3 murine fibroblasts dosed with vehicle control and with three ricin concentrations. At the time of sample collection (48 h post dosing), only attached cells were harvested. Adjustment was made for cell concentration in preparing samples for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Analysis of the LC-MS/MS data to determine peptide sequences, followed by statistical filtering, has shown that at least one 3T3 peptide biomarker exists for each biological cell group (vehicle control and 3 ricin dose levels). These peptides correspond to particular proteins expressed by the 3T3 cells. Identification of the relevant proteins, followed by metabolic pathway analysis to determine the pathways in which those proteins are involved, may reveal the survival mechanism for cells dosed at low levels, which in turn will provide insight into the related 3T3 physiological changes required to overcome ricin dosing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2011
- Accession Number
- ADA546022
Entities
People
- Janna S. Madren-whalley
- Jeffrey S. Rice
- Kyle Jones
- Lisa M. Reilly
- Rabih E. Jabbour
- Samir Deshpande
- Vicky L.H. Bevilacqua
Organizations
- Edgewood Chemical Biological Center