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

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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 γradiation 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, N 1-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.

Original languageEnglish (US)
Pages (from-to)473-484
Number of pages12
JournalRadiation research
Volume175
Issue number4
DOIs
StatePublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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