Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice

John B. Tyburski, Andrew D. Patterson, Kristopher W. Krausz, Josef Slavík, Albert J. Fornace, Frank J. Gonzalez, Jeffrey R. Idle

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Gamma-radiation exposure has both short- and long-term adverse health effects. The threat of modern terrorism places human populations at risk for radiological exposures, yet current medical countermeasures to radiation exposure are limited. Here we describe metabolomics for γ-radiation biodosimetry in a mouse model. Mice were γ-irradiated at doses of 0, 3 and 8 Gy (2.57 Gy/min), and urine samples collected over the first 24 h after exposure were analyzed by ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). Multivariate data were analyzed by orthogonal partial least squares (OPLS). Both 3- and 8-Gy exposures yielded distinct urine metabolomic phenotypes. The top 22 ions for 3 and 8 Gy were analyzed further, including tandem mass spectrometric comparison with authentic standards, revealing that N-hexanoylglycine and β-thymidine are urinary biomarkers of exposure to 3 and 8 Gy, 3-hydroxy-2-methylbenzoic acid 3-O-sulfate is elevated in urine of mice exposed to 3 but not 8 Gy, and taurine is elevated after 8 but not 3 Gy. Gene Expression Dynamics Inspector (GEDI) self-organizing maps showed clear dose-response relationships for subsets of the urine metabolome. This approach is useful for identifying mice exposed to γ radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalRadiation research
Volume170
Issue number1
DOIs
Publication statusPublished - Jul 1 2008

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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