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Radiation and Environmental Biophysics

, Volume 53, Issue 4, pp 645–657 | Cite as

The effect of low dose rate on metabolomic response to radiation in mice

  • Maryam Goudarzi
  • Tytus D. Mak
  • Congju Chen
  • Lubomir B. Smilenov
  • David J. Brenner
  • Albert J. FornaceEmail author
Original Paper

Abstract

Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual’s exposure in a radiobiological event and thus would have utility for both triage and injury assessment.

Keywords

Metabolomics Low dose rate radiation Mass spectrometry 

Notes

Acknowledgments

This study was supported by the National Institute of Health (National Institute of Allergy and Infectious Diseases) grant U19 A1067773. The authors would like to thank Georgetown University’s Proteomic and Metabolomics Shared Resources, NIH P30 CA51008, for providing access to mass spectrometry and related resources. We would also like to acknowledge the efforts of Steven Strawn in obtaining pure chemical standards and Yue Luo and Rajbir Sohi in mass spectrometry.

Supplementary material

411_2014_558_MOESM1_ESM.tif (191 kb)
Time-dependent urinary metabolomic profiles of 1.1 Gy HDR exposed mice shown in panels A (heatmap) and B (PCA) created in RF. Similar plots are shown for 1.1 Gy LDR exposure in panels C and D. The time-points are 2 days and 5 days post 1.1 Gy irradiation. The numbered boxes on each heatmap highlight specific groups of metabolites with respect to the unique changes in their urinary excretion levels at these 2 time-points. Box 1 in both panels A and C show metabolites whose levels progressively decrease from day 2 to day 5 post exposure. Box 2 in panel A shows IR responsiveness of a few metabolites spiked at day 2 but dissipates by day 5 to that of controls. Box 3 in both panels A and C show ions whose levels steadily increase post IR exposure at days 2 and 5 with respect to control levels. Box 4 in panel A shows a few metabolites whose levels do not show any significant changes until 5 days post exposure. These distinct groups of metabolites contribute to the separation of overall metabolomic signatures of day 2 and day 5 urines Supplementary material 1 (TIFF 191 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Maryam Goudarzi
    • 1
  • Tytus D. Mak
    • 2
  • Congju Chen
    • 3
  • Lubomir B. Smilenov
    • 3
  • David J. Brenner
    • 3
  • Albert J. Fornace
    • 1
    • 2
    Email author
  1. 1.Biochemistry and Molecular and Cellular BiologyGeorgetown UniversityWashingtonUSA
  2. 2.Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA
  3. 3.Center for High-Throughput Minimally-Invasive Radiation BiodosimetryColumbia UniversityNew YorkUSA

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