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Herein, we introduce a strategy for assessment of the impact of radiation\u2010induced oxidative stress on the intra\u2010cellular metabolism of human leukocytes. Untargeted metabolomic analyses were performed by CE\u2010ESI\u2010MS on irradiated leukocytes exposed to increasing doses of \u2010radiation emitted from a Taylor source, which were subsequently incubated for 44\u2009h to allow for cellular recovery. Flow cytometry with dual fluorescence staining revealed a major shift from early\u2010 to late\u2010stage apoptosis associated with cell membrane permeability changes as radiation dosage was increased relative to the control, but with a significant attenuation measured at intermediate dose levels. CE\u2010ESI\u2010MS analysis of filtered white blood cell lysates was also performed to quantify changes associated with 22 intra\u2010cellular metabolites, which were consistently measured in leukocytes across all radiation levels. Preliminary experiments demonstrated that there was an overall depletion in metabolites with extended exposure to IR; however, there was a non\u2010linear upregulation of specific metabolites at the 4\u2009Gy level relative to pre\u2010irradiated levels, notably for arginine, glutamine, creatine, proline and reduced glutathione. Our studies demonstrate that leukocytes require a minimum threshold level of IR to induce a cytoprotective response in metabolism associated with antioxidant defense, energy homeostasis and cell signaling, which is relevant to improved understanding of the mechanisms of oxidative stress in radiobiology and cancer therapy.<\/jats:p>","DOI":"10.1002\/elps.200900451","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T07:48:34Z","timestamp":1277106514000},"page":"2328-2337","source":"Crossref","is-referenced-by-count":24,"title":["Metabolomic studies of radiation\u2010induced apoptosis of human leukocytes by capillary electrophoresis\u2010mass spectrometry and flow cytometry: Adaptive cellular responses to ionizing radiation"],"prefix":"10.1002","volume":"31","author":[{"given":"Richard","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Britz\u2010McKibbin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0960327108098493"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/421691a"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.01.001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/10915810802503735"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/713611045"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.2307\/3579806"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/01948454"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-006-0191-5"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004032-200307000-00011"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.2307\/3579809"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.45.357"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.05.003"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7572"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(96)00554-0"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.07.007"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2007.07.005"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-008-0167-z"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR0689.1"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.07022"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR0487.1"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(97)00357-X"},{"key":"e_1_2_6_23_2","first-page":"339","volume":"50","author":"Woloschak G. 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