UPLC-ESI-QTOFMS-based metabolomics for urinary biomarker discovery in gamma-irradiated rats

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	OXIDSTRESS-4

Authors

• C Johnson
• A Patterson
• K Krausz
• C Lanz
• D Kang
• H Luecke
• F Gonzalez
• J Idle

Abstract

Identifying noninvasive biomarkers of ionizing radiation would permit rapid assessment and triage of exposed individuals for palliative and follow-up care. It may also facilitate the elucidation of novel molecular mechanisms associated with the ionizing radiation DNA damage and repair response. Radiation metabolomics has aided in identification of biomarkers in cells and mice by UPLC-ESI-QTOFMS, and in rats by GC-MS. UPLC-ESI-QTOFMS was used here to analyze rat urine samples taken from 12 rats over seven days; they were either sham-irradiated or gamma-irradiated with 3 Gy after four days of metabolic cage acclimatization. Using multivariate data analysis, nine urinary biomarkers of gamma-ionizing radiation in rats were discovered including a novel mammalian metabolite, N-acetyltaurine. These up-regulated 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 GC-MS and in the mouse. 2’-Deoxyxanthosine, taurine and N-hexanoylglycine were also seen in the mouse. These are now unequivocal cross-species biomarkers for ionizing gamma-radiation exposure. The UPLC-ESI-QTOFMS approach has aided in the advance for finding common ionizing gamma-radiation exposure biomarkers.

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