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Targeted Metabolomics Reveals Metabolomic Signatures Correlating Gastrointestinal Tissue to Plasma in a Mouse Total-body Irradiation Model

Jones, Jace W.1; Clifford, Zachary1; Li, Fei1; Tudor, Gregory L.2; Farese, Ann M.3; Booth, Catherine2; MacVittie, Thomas J.3; Kane, Maureen A.1

doi: 10.1097/HP.0000000000000955
BIOMARKERS: A MULTIDISCIPLINARY APPROACH: PAPERS
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High-throughput, targeted metabolomics was used to identify early time-point small intestine and plasma metabolite markers of gastrointestinal acute radiation syndrome. The small intestine metabolite markers were cross correlated to plasma metabolites in order to identify minimally invasive circulating markers. The radiation exposure covered lethal and sublethal gastrointestinal acute radiation syndrome. The small intestine and plasma metabolite profiles were generated at 1 and 3 d postexposure following total-body irradiation. The small intestine and plasma metabolite profiles for mice receiving radiation at day 1 and 3 postexposure were significantly different from sham-irradiated mice. There were 14 metabolite markers identified at day 1 and 18 metabolite markers at day 3 that were small-intestine-specific plasma markers of gastrointestinal acute radiation syndrome. A number of the identified metabolites at day 1 were amino acids. Dysregulation of amino acid metabolism at 24 h post-total-body irradiation provides potential insight into the initial inflammatory response during gastrointestinal acute radiation syndrome.

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.

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 3 July 2018)

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© 2019 by the Health Physics Society