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Int. J. Mol. Sci. 2016, 17(5), 782; doi:10.3390/ijms17050782

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

1
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20057, USA
2
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20057, USA
3
Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA
4
Center for Radiological Research, Columbia University, 630 West 168th Street, VC11-240, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 12 January 2016 / Revised: 23 March 2016 / Accepted: 10 May 2016 / Published: 20 May 2016
(This article belongs to the Section Molecular Pathology)
View Full-Text   |   Download PDF [4005 KB, uploaded 26 May 2016]   |  

Abstract

With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs) and Strontium-90 (90Sr). The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation. View Full-Text
Keywords: Internal emitters; X-ray irradiation; quantitative metabolomics; multiple reaction monitoring; calcitroic acid; citrulline; biodosimetry Internal emitters; X-ray irradiation; quantitative metabolomics; multiple reaction monitoring; calcitroic acid; citrulline; biodosimetry
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MDPI and ACS Style

Goudarzi, M.; Chauthe, S.; Strawn, S.J.; Weber, W.M.; Brenner, D.J.; Fornace, A.J. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation. Int. J. Mol. Sci. 2016, 17, 782.

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