Linked Life Data

16910775

Source:http://linkedlifedata.com/resource/pubmed/id/16910775

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pubmed-article:16910775pubmed:dateCreated2006-8-16lld:pubmed
pubmed-article:16910775pubmed:abstractTextThis study investigates the hypothesis that Mn-superoxide dismutase (MnSOD) influences cancer cell radiosensitivity by regulating the G(2)-checkpoint pathway. Human oral squamous carcinoma cells (SCC25) stably overexpressing MnSOD were irradiated (6 Gy) and assayed for cell survival, cell-cycle phase distributions, and bromodeoxyuridine (BrdU) pulse-chase flow-cytometric measurements of cell-cycle phase transits. Electron paramagnetic resonance (EPR) spectroscopy was used to measure steady-state levels of oxygen-centered free radicals. Glutathione and glutathione disulfide levels were used as indicators of changes in the intracellular redox state. MnSOD overexpression increased radioresistance threefold to fourfold; this increase was associated with twofold to threefold increases in radiation-induced G(2) accumulation. BrdU pulse-chase and flow-cytometric measurements of the percentage of G(1) and relative movement showed no significant changes in G(1) and S transits; however, the percentage of G(2) cells and BrdU-positive cells showed delayed G(2)+M transits in MnSOD-overexpressing irradiated cells. The steady-state levels of oxygen-centered free radicals were not significantly different in vector compared with MnSOD-overexpressing cells, suggesting that the free radical generation is essentially similar. MnSOD overexpression did prevent radiation-induced decreases in total glutathione content, which correlated with radioresistance and enhanced G(2) accumulation. These results support the hypothesis that a "metabolic redox-response" to IR exposure regulates radiosensitivity by altering radiation-induced G(2) accumulation.lld:pubmed
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pubmed-article:16910775pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:16910775pubmed:articleTitleMn-superoxide dismutase overexpression enhances G2 accumulation and radioresistance in human oral squamous carcinoma cells.lld:pubmed
pubmed-article:16910775pubmed:affiliationFree Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, 52242, USA.lld:pubmed
pubmed-article:16910775pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16910775pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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