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10 February 2011 Radiation Metabolomics. 4. UPLC-ESI-QTOFMS-Based Metabolomics for Urinary Biomarker Discovery in Gamma-Irradiated Rats
Caroline H Johnson, Andrew D Patterson, Kristopher W Krausz, Christian Lanz, Dong Wook Kang, Hans Luecke, Frank J Gonzalez, Jeffrey R Idle
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Abstract

Radiation metabolomics has aided in the identification of a number of biomarkers in cells and mice by ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and in rats by gas chromatography-coupled mass spectrometry (GCMS). These markers have been shown to be both dose- and time-dependent. Here UPLC-ESI-QTOFMS was used to analyze rat urine samples taken from 12 rats over 7 days; they were either sham-irradiated or γ-irradiated with 3 Gy after 4 days of metabolic cage acclimatization. Using multivariate data analysis, nine urinary biomarkers of γ radiation in rats were identified, including a novel mammalian metabolite, N-acetyltaurine. These upregulated urinary biomarkers were confirmed through tandem mass spectrometry and comparisons with authentic standards. They include thymidine, 2′-deoxyuridine, 2′deoxyxanthosine, N1-acetylspermidine, N-acetylglucosamine/galactosamine-6-sulfate, N-acetyltaurine, N-hexanoylglycine, taurine and, tentatively, isethionic acid. Of these metabolites, 2′-deoxyuridine and thymidine were previously identified in the rat by GCMS (observed as uridine and thymine) and in the mouse by UPLC-ESI-QTOFMS. 2′Deoxyxanthosine, taurine and N-hexanoylglycine were also seen in the mouse by UPLC-ESI-QTOFMS. These are now unequivocal cross-species biomarkers for ionizing radiation exposure. Downregulated biomarkers were shown to be related to food deprivation and starvation mechanisms. The UPLC-ESI-QTOFMS approach has aided in the advance for finding common biomarkers of ionizing radiation exposure.

by Radiation Research Society
Caroline H Johnson, Andrew D Patterson, Kristopher W Krausz, Christian Lanz, Dong Wook Kang, Hans Luecke, Frank J Gonzalez, and Jeffrey R Idle "Radiation Metabolomics. 4. UPLC-ESI-QTOFMS-Based Metabolomics for Urinary Biomarker Discovery in Gamma-Irradiated Rats," Radiation Research 175(4), 473-484, (10 February 2011). https://doi.org/10.1667/RR2437.1
Received: 6 September 2010; Accepted: 1 December 2010; Published: 10 February 2011
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