Journal article
Mn-Superoxide Dismutase Overexpression Enhances G2 Accumulation and Radioresistance in Human Oral Squamous Carcinoma Cells
Antioxidants & redox signaling, Vol.8(7-8), pp.1273-1281
07/2006
DOI: 10.1089/ars.2006.8.1273
PMID: 16910775
Abstract
This 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.
Details
- Title: Subtitle
- Mn-Superoxide Dismutase Overexpression Enhances G2 Accumulation and Radioresistance in Human Oral Squamous Carcinoma Cells
- Creators
- Amanda L Kalen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IowaEhab H Sarsour - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IowaSujatha Venkataraman - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IowaPrabhat C Goswami - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.8(7-8), pp.1273-1281
- DOI
- 10.1089/ars.2006.8.1273
- PMID
- 16910775
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Language
- English
- Date published
- 07/2006
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047682402771
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