title: Identification and quantitation of biomarkers for radiation-induced injury via mass spectrometry.
abstract: Biomarker identification and validation for radiation exposure is a rapidly expanding field encompassing the need for well defined animal models and advanced analytical techniques. The resources within the consortium, Medical Countermeasures Against Radiological Threats (MCART), provide a unique opportunity for accessing well defined animal models that simulate the key sequelae of the acute radiation syndrome and the delayed effects of acute radiation exposure. Likewise, the use of mass spectrometry-based analytical techniques for biomarker discovery and validation enables a robust analytical platform that is amenable to a variety of sample matrices and considered the benchmark for biomolecular identification and quantitation. Herein, the authors demonstrate the use of two targeted mass spectrometry approaches to link established MCART animal models to identified metabolite biomarkers. Circulating citrulline concentration was correlated to gross histological gastrointestinal tissue damage, and retinoic acid production in lung tissue was established to be reduced at early and late time points post high dose irradiation. Going forward, the use of mass spectrometry-based metabolomics coupled to well defined animal models provides the unique opportunity for comprehensive biomarker discovery.
authors.affiliation: *University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD; †University of Maryland, School of Dentistry, Department of Microbial Pathogenesis, Baltimore, MD; ‡Epistem Ltd, Manchester, UK; §University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.
authors.forename: Jace W
authors.initials: JW
authors.lastname: Jones
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Scott
authors.forename: Gregory
authors.initials: G
authors.lastname: Tudor
authors.forename: Pu-Ting
authors.initials: PT
authors.lastname: Xu
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Jackson
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Catherine
authors.initials: C
authors.lastname: Booth
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kane
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002956:Citrulline / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002956:Citrulline; D014212:Tretinoin