Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance
| Autor: | Catherine R. Mitchell, Michael C. Joiner, Brian Marples, N. E. Cann, Peter J. Johnston |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
DNA Repair
DNA repair Cell Survival Blotting Western Cell Separation DNA-Activated Protein Kinase Biology Protein Serine-Threonine Kinases Radiation Tolerance Flow cytometry Radioresistance medicine Tumor Cells Cultured Humans Radiology Nuclear Medicine and imaging Radiosensitivity Nuclear protein Protein kinase A Radiological and Ultrasound Technology medicine.diagnostic_test X-Rays Nuclear Proteins Dose-Response Relationship Radiation Cell sorting Models Theoretical Flow Cytometry Molecular biology DNA-Binding Proteins Biochemistry Cell culture Regression Analysis |
| Zdroj: | International journal of radiation biology. 78(12) |
| ISSN: | 0955-3002 |
| Popis: | To investigate the role of DNA-dependent protein kinase (DNA-PK) in the phenomena of low dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR) using the genetically related M059 cell lines of disparate PRKDC status.Clonogenic survival was measured for the three cell lines following low doses of X-irradiation using a flowactivated cell sorting (FACS) plating technique. The presence of PRKDC, G22p1 and Xrcc5 proteins was determined by Western blotting and a kinase assay used to measure DNA-PK complex activity.The survival responses for the three cell lines over the 0-0.3Gy dose range were comparable, but differences in radiosensitivity were evident at doses0.4Gy. M059K and M059J/Fus1 cells (both PRKDC competent) exhibited marked HRS/IRR responses, albeit to different extents. M059J cells (PRKDC incompetent) were extremely radiosensitive exhibiting a linear survival curve with no evidence of IRR. The presence of IRR was coincident with the presence of PRKDC protein and functional DNA-PK activity.HRS is a response that is independent of DNA-PK activity. In contrast, IRR showed a dependence on the presence of PRKDC protein and functional DNA-PK activity. These data support a role for DNA-PK activity in the IRR response. |
| Databáze: | OpenAIRE |
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