title: A Comprehensive Metabolomic Investigation in Urine of Mice Exposed to Strontium-90.
abstract: Internal emitters such as Strontium-90 ((90)Sr) pose a substantial health risk during and immediately after a nuclear disaster or detonation of an improvised device. The environmental persistency and potency of (90)Sr calls for urgent development of high-throughput tests to establish levels of exposure and to help triage potentially exposed individuals who were in the immediate area of the disaster. In response to these concerns, our team focused on developing a robust metabolomic profile for (90)Sr exposure in urine using a mouse model. The sensitivity of modern time-of-flight mass spectrometry (TOFMS) combined with the separation power of ultra performance liquid chromatography (UPLC) was used to determine perturbations in the urinary metabolome of mice exposed to (90)Sr. The recently developed statistical suite, MetaboLyzer, was used to explore the mass spectrometry data. The results indicated a significant change in the urinary abundances of metabolites pertaining to butanoate metabolism, vitamin B metabolism, glutamate and fatty acid oxidation. All of these pathways are either directly or indirectly connected to the central energy production pathway, the tricarboxylic acid (TCA) cycle. To our knowledge, this is the first in vivo metabolomics to evaluate the effects of exposure to (90)Sr using the easily accessible biofluid, urine.
authors.affiliation: a  Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C.;
authors.forename: Maryam
authors.initials: M
authors.lastname: Goudarzi
authors.affiliation: b  Lovelace Respiratory Research Institute, Albuquerque, New Mexico;
authors.forename: Waylon M
authors.initials: WM
authors.lastname: Weber
authors.affiliation: c  Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, Maryland; and.
authors.forename: Tytus D
authors.initials: TD
authors.lastname: Mak
authors.affiliation: a  Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C.;
authors.forename: Juijung
authors.initials: J
authors.lastname: Chung
authors.affiliation: b  Lovelace Respiratory Research Institute, Albuquerque, New Mexico;
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.affiliation: b  Lovelace Respiratory Research Institute, Albuquerque, New Mexico;
authors.forename: Dunstana R
authors.initials: DR
authors.lastname: Melo
authors.affiliation: a  Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C.;
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Strawn
authors.affiliation: d  Center for Radiological Research, Columbia University, New York, New York.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brenner
authors.affiliation: b  Lovelace Respiratory Research Institute, Albuquerque, New Mexico;
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Guilmette
authors.affiliation: a  Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C.;|c  Mass Spectrometry Data Center, National Institute of Standards and Technology, Gaithersburg, Maryland; and.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D004307:Dose-Response Relationship, Radiation; D055432:Metabolomics; D051379:Mice; D013326:Strontium Radioisotopes / Q000009:adverse effects; D013997:Time Factors; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D013326:Strontium Radioisotopes