Radiation metabolomics and its potential in biodosimetry

Abstract

Purpose: Radiation exposure triggers a complex network of molecular and cellular responses that impacts metabolic processes and alters the levels of metabolites. Such metabolites have potential as biomarkers for radiation dosimetry. This review provides an overview of radiation signalling and metabolism, of metabolomic approaches used in the discovery phase, and of instrumentation with the potential to assess radiation injury in the field.

Approach: Recent developments in fast, high-resolution chromatography and mass spectrometry and new data analysis methods allow the quantitative assessment of thousands of metabolites based on biofluids obtained non-invasively. This complex analysis leads to the discovery-phase identification of groups of metabolites useful for screening and biodosimetry by targeted quantitative measurement. Instrumentation for target analysis can be simpler than that used for discovery, so we examine current technologies based on ion mobility.

Conclusions: Recent published results and ongoing studies examine the complex changes in the levels of many metabolites caused by radiation exposure, and identify groups of small-molecule biomarkers for radiation biodosimetry. Based on results showing separation orthogonal to mass, chemical noise suppression, and high sensitivity, differential mobility mass spectrometry (DMS-MS) ion mobility spectrometry appears highly promising for the development of deployable instrumentation.

Keywords:

• radiation biodosimetry
• metabolomics
• metabonomics
• mass spectrometry
• ion mobility
• differential mobility
• DMS
• DMS-MS

Acknowledgements

The authors would like to acknowledge Dr David J. Brenner and Dr Frank J. Gonzalez for their support. Some of the authors, SLC, JBT, ECL, and AJF, were supported as part of the Columbia Center for High-Throughput Minimally Invasive Radiation Biodosimetry (P.I. David Brenner) and funded by NIH (NIAID) grant U19 AI067773. Efforts by AJF were also supported in part by grant R31-10069 (WCU program) through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.