UPLC-ESI-TOFMS-Based Metabolomics and Gene Expression Dynamics Inspector Self-Organizing Metabolomic Maps as Tools for Understanding the Cellular Response to Ionizing Radiation
- 4 January 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Analytical Chemistry
- Vol. 80 (3), 665-674
- https://doi.org/10.1021/ac701807v
Abstract
Global transcriptomic and proteomic profiling platforms have yielded important insights into the complex response to ionizing radiation (IR). Nonetheless, little is known about the ways in which small cellular metabolite concentrations change in response to IR. Here, a metabolomics approach using ultraperformance liquid chromatography coupled with electrospray time-of-flight mass spectrometry was used to profile, over time, the hydrophilic metabolome of TK6 cells exposed to IR doses ranging from 0.5 to 8.0 Gy. Multivariate data analysis of the positive ions revealed dose- and time-dependent clustering of the irradiated cells and identified certain constituents of the water-soluble metabolome as being significantly depleted as early as 1 h after IR. Tandem mass spectrometry was used to confirm metabolite identity. Many of the depleted metabolites are associated with oxidative stress and DNA repair pathways. Included are reduced glutathione, adenosine monophosphate, nicotinamide adenine dinucleotide, and spermine. Similar measurements were performed with a transformed fibroblast cell line, BJ, and it was found that a subset of the identified TK6 metabolites were effective in IR dose discrimination. The GEDI (Gene Expression Dynamics Inspector) algorithm, which is based on self-organizing maps, was used to visualize dynamic global changes in the TK6 metabolome that resulted from IR. It revealed dose-dependent clustering of ions sharing the same trends in concentration change across radiation doses. “Radiation metabolomics,” the application of metabolomic analysis to the field of radiobiology, promises to increase our understanding of cellular responses to stressors such as radiation.Keywords
This publication has 48 references indexed in Scilit:
- Metabolomic and Genetic Analysis of Biomarkers for Peroxisome Proliferator-Activated Receptor α Expression and ActivationMolecular Endocrinology, 2007
- Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometryBMC Bioinformatics, 2007
- A Comprehensive Investigation of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Metabolism in the Mouse Using a Multivariate Data Analysis ApproachChemical Research in Toxicology, 2007
- Urinary Metabolite Profiling Reveals CYP1A2-Mediated Metabolism of NSC686288 (Aminoflavone)The Journal of pharmacology and experimental therapeutics, 2006
- A Metabolomic Approach to the Metabolism of the Areca Nut Alkaloids Arecoline and Arecaidine in the MouseChemical Research in Toxicology, 2006
- An integrated systems approach for understanding cellular responses to gamma radiationMolecular Systems Biology, 2006
- NAD+ Consumption in Carcinogen-Treated Hamster Cells Overexpressing a Dominant Negative Mutant of Poly(ADP-ribose) PolymeraseBiochemical and Biophysical Research Communications, 1999
- Fishing ExpeditionsScience, 1998
- Postirradiation administration of adenosine monophosphate combined with dipyridamole reduces early cellular damage in miceLife Sciences, 1993
- Protection of early cellular damage in 1 Gy-irradiated mice by the elevation of extracellular adenosineRadiation and Environmental Biophysics, 1992