Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Jones JW

PROVIDER: S-EPMC6384130 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Jones Jace W JW Clifford Zachary Z Li Fei F Tudor Gregory L GL Farese Ann M AM Booth Catherine C MacVittie Thomas J TJ Kane Maureen A MA

Health physics 20190401 4

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 ...[more]

PMID: 30624349

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Project description:The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4-6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher's exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid ?-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker identification based on the overlap between animal models and humans.

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Dataset Information

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

Publications

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

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