Metabolomics

, Volume 11, Issue 5, pp 1082–1094

Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat

  • Tytus D. Mak
  • John B. Tyburski
  • Kristopher W. Krausz
  • John F. Kalinich
  • Frank J. Gonzalez
  • Albert J. FornaceJr.
Original Article

DOI: 10.1007/s11306-014-0765-4

Cite this article as:
Mak, T.D., Tyburski, J.B., Krausz, K.W. et al. Metabolomics (2015) 11: 1082. doi:10.1007/s11306-014-0765-4

Abstract

The potential for exposures to ionizing radiation (IR) has increased in recent years. Although advances have been made, understanding the global metabolic response as a function of both dose and exposure time is challenging considering the complexity of the responses. Herein we report our findings on the dose- and time-dependency of the urinary response to IR in the male rat using radiation metabolomics. Urine samples were collected from adult male rats, exposed to 0.5–10 Gy γ-radiation, both before from 6 to 72 h following exposures. Samples were analyzed by liquid chromatography coupled with time-of-flight mass spectrometry, and deconvoluted mass chromatographic data were initially analyzed by principal component analysis. However, the breadth and complexity of the data necessitated the development of a novel approach to summarizing biofluid constituents after exposure, called Visual Analysis of Metabolomics Package (VAMP). VAMP revealed clear urine metabolite profile differences to as little as 0.5 Gy after 6 h exposure. Via VAMP, it was discovered that the response to radiation exposure found in rat urine is characterized by an overall net down-regulation of ion excretion with only a modest number of ions excreted in excess over pre-exposure levels. Our results show both similarities and differences with the published mouse urine response and a dose- and time-dependent net decrease in urine ion excretion associated with radiation exposure. These findings mark an important step in the development of minimally invasive radiation biodosimetry. VAMP should have general applicability in metabolomics to visualize overall differences and trends in many sample sets.

Keywords

Radiation Biodosimetry Bioinformatics 

Abbreviations

DMS–MS

Differential mobility spectrometry–mass spectrometry

AFRRI

Armed Forces Radiobiology Research Institute

MS

Mass spectrometer

UPLC–TOFMS

Ultra-performance liquid chromatography–time of flight mass spectrometry

ESI

Electrospray ionization

ESI+

Positive ESI

ESI−

Negative ESI

PCA

Principal component analysis

PC

Principal component

IR

Ionizing radiation

IS

Internal standard

ppm

Parts per million

CI

Confidence interval

VAMP

Visual Analysis of Metabolomics Package

Supplementary material

11306_2014_765_MOESM1_ESM.docx (4.3 mb)
Supplementary material 1 (DOCX 4374 kb)
11306_2014_765_MOESM2_ESM.docx (12 kb)
Supplementary material 2 (DOCX 11 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Tytus D. Mak
    • 1
  • John B. Tyburski
    • 2
  • Kristopher W. Krausz
    • 3
  • John F. Kalinich
    • 4
  • Frank J. Gonzalez
    • 3
  • Albert J. FornaceJr.
    • 1
    • 2
  1. 1.Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonUSA
  2. 2.Biochemistry and Molecular & Cellular BiologyGeorgetown University Medical CenterWashingtonUSA
  3. 3.Laboratory of Metabolism, Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  4. 4.Armed Forces Radiobiology Research InstituteUniformed Services UniversityBethesdaUSA