title: Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing radiation exposure in nonhuman primates by mass spectrometry-based metabolomics.
abstract: Mass spectrometry-based metabolomics has previously demonstrated utility for identifying biomarkers of ionizing radiation exposure in cellular, mouse and rat in vivo radiation models. To provide a valuable link from small laboratory rodents to humans, γ-radiation-induced urinary biomarkers were investigated using a nonhuman primate total-body-irradiation model. Mass spectrometry-based metabolomics approaches were applied to determine whether biomarkers could be identified, as well as the previously discovered rodent biomarkers of γ radiation. Ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry analysis was carried out on a time course of clean-catch urine samples collected from nonhuman primates (n = 6 per cohort) exposed to sham, 1.0, 3.5, 6.5 or 8.5 Gy doses of (60)Co γ ray (∼0.55 Gy/min) ionizing radiation. By multivariate data analysis, 13 biomarkers of radiation were discovered: N-acetyltaurine, isethionic acid, taurine, xanthine, hypoxanthine, uric acid, creatine, creatinine, tyrosol sulfate, 3-hydroxytyrosol sulfate, tyramine sulfate, N-acetylserotonin sulfate, and adipic acid. N-Acetyltaurine, isethionic acid, and taurine had previously been identified in rats, and taurine and xanthine in mice after ionizing radiation exposure. Mass spectrometry-based metabolomics has thus successfully revealed and verified urinary biomarkers of ionizing radiation exposure in the nonhuman primate for the first time, which indicates possible mechanisms for ionizing radiation injury.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 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: John F
authors.initials: JF
authors.lastname: Kalinich
authors.forename: John B
authors.initials: JB
authors.lastname: Tyburski
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: William F
authors.initials: WF
authors.lastname: Blakely
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Idle
mesh_terms: D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D008253:Macaca mulatta; D008297:Male; D055432:Metabolomics; D051379:Mice; D011832:Radiation Injuries / Q000652:urine*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers