Radiation metabolomics and its potential in biodosimetry

被引:81
作者
Coy, Stephen L. [1 ,2 ]
Cheema, Amrita K. [3 ]
Tyburski, John B. [1 ,2 ]
Laiakis, Evagelia C. [1 ,2 ]
Collins, Sean P. [3 ,4 ]
Fornace, Albert J., Jr. [1 ,2 ,3 ]
机构
[1] Georgetown Univ, Dept Biochem, Washington, DC 20057 USA
[2] Georgetown Univ, Dept Mol & Cellular Biol, Washington, DC 20057 USA
[3] Georgetown Univ, Dept Oncol, Washington, DC 20057 USA
[4] Georgetown Univ, Dept Radiat Med, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA
关键词
radiation biodosimetry; metabolomics; metabonomics; mass spectrometry; ion mobility; differential mobility; DMS; DMS-MS; SPECTROMETRY-BASED METABOLOMICS; NF-KAPPA-B; MASS-SPECTROMETRY; GENE-EXPRESSION; IONIZING-RADIATION; TUMOR-SUPPRESSOR; BIOMARKER DISCOVERY; SEPARATION PROCESS; STRESS GENES; P53;
D O I
10.3109/09553002.2011.556177
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:802 / 823
页数:22
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