title: Late ROS accumulation and radiosensitivity in SOD1-overexpressing human glioma cells.
abstract: This study investigates the hypothesis that CuZn superoxide dismutase (SOD1) overexpression confers radioresistance to human glioma cells by regulating the late accumulation of reactive oxygen species (ROS) and the G(2)/M-checkpoint pathway. U118-9 human glioma cells (wild type, neo vector control, and stably overexpressing SOD1) were irradiated (0-10 Gy) and assayed for cell survival, cellular ROS levels, cell-cycle-phase distributions, and cyclin B1 expression. SOD1-overexpressing cells were radioresistant compared to wild-type (wt) and neo vector control (neo) cells. Irradiated wt and neo cells showed a significant increase (approximately twofold) in DHE fluorescence beginning at 2 days postirradiation, which remained elevated at 8 days postirradiation. Interestingly, the late accumulation of ROS was suppressed in irradiated SOD1-overexpressing cells. The increase in ROS levels was followed by a decrease in cell growth and viability and an increase in the percentage of cells with sub-G(1) DNA content. SOD1 overexpression enhanced radiation-induced G(2) accumulation within 24 h postirradiation, which was accompanied by a decrease in cyclin B1 mRNA and protein levels. These results support the hypothesis that long after radiation exposure a "metabolic redox response" regulates radiosensitivity of human glioma cells.
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.forename: Ehab H
authors.initials: EH
authors.lastname: Sarsour
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Kalen
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Maneesh G
authors.initials: MG
authors.lastname: Kumar
authors.forename: Prabhat C
authors.initials: PC
authors.lastname: Goswami
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D016195:G2 Phase / Q000528:radiation effects; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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