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Proteomic Evaluation of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Murine Total-body Irradiation Model

Huang, Weiliang1; Yu, Jianshi1; Jones, Jace W.1; Carter, Claire L.1; Pierzchalski, Keely1; Tudor, Gregory2; Booth, Catherine2; MacVittie, Thomas J.3; Kane, Maureen A.1

doi: 10.1097/HP.0000000000000951
BIOMARKERS: A MULTIDISCIPLINARY APPROACH: PAPERS
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Radiation exposure to the gastrointestinal system contributes to the acute radiation syndrome in a dose- and time-dependent manner. Molecular mechanisms that lead to the gastrointestinal acute radiation syndrome remain incompletely understood. Using a murine model of total-body irradiation, C57BL/6J male mice were irradiated at 8, 10, 12, and 14 Gy and assayed at day 1, 3, and 6 after exposure and compared to nonirradiated (sham) controls. Tryptic digests of gastrointestinal tissues (upper ileum) were analyzed by liquid chromatography-tandem mass spectrometry on a Waters nanoLC coupled to a Thermo Scientific Q Exactive hybrid quadrupole-orbitrap mass spectrometer. Pathway and gene ontology analysis were performed with Qiagen Ingenuity, Panther GO, and DAVID databases. A number of trends were identified in our proteomic data including pronounced protein changes as well as protein changes that were consistently up regulated or down regulated at all time points and dose levels interrogated. Time- and dose-dependent protein changes, canonical pathways affected by irradiation, and changes in proteins that serve as upstream regulators were also identified. Additionally, proteins involved in key processes including inflammation, radiation, and retinoic acid signaling were identified. The proteomic profiling conducted here represents an untargeted systems biology approach to identify acute molecular events that will be useful for a greater understanding of animal models and may be potentially useful toward the development of medical countermeasures and/or biomarkers.

1University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD;

2Epistem Ltd., Manchester, UK;

3University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.

The authors declare no conflicts of interest.

For correspondence contact Maureen A. Kane, University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, 20 N. Pine Street, Room 723, Baltimore, MD 21201, or email at mkane@rx.umaryland.edu.

(Manuscript accepted 4 July 2018)

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© 2019 by the Health Physics Society