Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice.
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 gamma-radiation biodosimetry in a mouse model. Mice were gamma-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 beta-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 gamma radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans.
Tyburski
John B
JB
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Patterson
Andrew D
AD
Krausz
Kristopher W
KW
Slavík
Josef
J
Fornace
Albert J
AJ
Gonzalez
Frank J
FJ
Idle
Jeffrey R
JR
D000818:Animals; D015415:Biomarkers / Q000652:urine; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010641:Phenotype; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000652:urine; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D013463:Sulfuric Acid Esters