title: Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer.
abstract: Nonlethal exposure to ionizing radiation (IR) is a public concern due to its known carcinogenic effects. Although latency periods for IR-induced neoplasms are relatively long, the ability to detect cancer as early as possible is highly advantageous for effective therapeutic intervention. Therefore, we hypothesized that metabolites in the urine from mice exposed to total body radiation (TBI) would predict for the presence of cancer before a palpable mass was detected. In this study, we exposed mice to 0 or 5.4 Gy TBI, collected urine samples periodically over 1 year, and assayed urine metabolites by using mass spectrometry. Longitudinal data analysis within the first year post-TBI revealed that cancers, including hematopoietic, solid, and benign neoplasms, could be distinguished by unique urinary signatures as early as 3 months post-TBI. Furthermore, a distinction among different types of malignancies could be clearly delineated as early as 3 months post-TBI for hematopoietic neoplasms, 6 months for solid neoplasms, and by 1 year for benign neoplasms. Moreover, the feature profile for radiation-exposed mice 6 months post-TBI was found to be similar to nonirradiated control mice at 18 months, suggesting that TBI accelerates aging. These results demonstrate that urine feature profiles following TBI can identify cancers in mice prior to macroscopic detection, with important implications for the early diagnosis and treatment.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Gadisetti V R
authors.initials: GV
authors.lastname: Chandramouli
authors.affiliation: Pathology/Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Anver
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, Bethesda, Maryland.
authors.forename: Angela
authors.initials: A
authors.lastname: Thetford
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, Bethesda, Maryland. james.mitchell3@nih.gov.
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.affiliation: Department of Veterinary and Biomedical Sciences and the Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D011839:Radiation, Ionizing; D014916:Whole-Body Irradiation / Q000379:methods