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Title: Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence ofmore » saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [3] ;  [5] ; ;  [6] ;  [3] ;  [4] ;  [1] ;  [2]
  1. Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States)
  2. (United States)
  3. Department of Medicine, Diabetes Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States)
  4. Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York (United States)
  5. Department of Pharmacology, Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York (United States)
  6. Department of Medicine, Oregon Health and Science University, Portland, Oregon (United States)
Publication Date:
OSTI Identifier:
22458603
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 91; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; ABSORBED RADIATION DOSES; BIOPSY; BLOOD PLASMA; CONCENTRATION RATIO; GAMMA RADIATION; GAS CHROMATOGRAPHY; IRRADIATION; LIPIDS; LIQUID COLUMN CHROMATOGRAPHY; LIVER; MASS SPECTROSCOPY; METABOLITES; MICE; PYRIMIDINES; RADIATION INJURIES; TRYPTOPHAN; URINE