title: Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.
abstract: Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Stephanie D
authors.identifier: http://orcid.org/0000-0002-9192-748X
authors.initials: SD
authors.lastname: Byrum
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Marie S
authors.initials: MS
authors.lastname: Burdine
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Orr
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.affiliation: CIToxLAB, Laval, Quebec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: CIToxLAB, Laval, Quebec, Canada.
authors.forename: Mylene
authors.initials: M
authors.lastname: Pouliot
authors.affiliation: Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000145:classification; D016000:Cluster Analysis; D004307:Dose-Response Relationship, Radiation; D004591:Electrophoresis, Polyacrylamide Gel; D005720:Gamma Rays; D008253:Macaca mulatta; D013058:Mass Spectrometry / Q000379:methods; D020543:Proteome / Q000145:classification / Q000528:radiation effects*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome