title: Radiation metabolomics. 4. UPLC-ESI-QTOFMS-Based metabolomics for urinary biomarker discovery in gamma-irradiated rats.
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, 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.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.forename: Christian
authors.initials: C
authors.lastname: Lanz
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Hans
authors.initials: H
authors.lastname: Luecke
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Idle
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D005720:Gamma Rays; D008297:Male; D055442:Metabolome / Q000528:radiation effects*; D020543:Proteome / Q000032:analysis* / Q000378:metabolism*; D011829:Radiation Dosage; D051381:Rats; D017208:Rats, Wistar; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D020543:Proteome