Differential Mechanisms of Cellular Radiobiological Response Following Exposure to Intensity Modulated Radiation Fields

Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and transformed fibroblast (AG0-1522) cells following exposure to modulated radiation fields created delivered using a X-Rad 225 kV X-ray generator. Uniform survival responses were compared to inand out-of-field responses in which 50% of the cell population was placed outside of the radiation field. Cell survival responses were determined under oxic and hypoxic conditions (0.1 % N2) and differential mechanisms of DNA damage response investigated use specific inhibitors of the DNA damage response pathway including ataxia telangiectasia mutated kinase (ATM, KU55933, Kudos Pharmaceuticals) and ataxia telangiectasia and Rad3-related protein kinase (ATR, Compound 45, Dr Chris Bakkenist, University of Pittsburgh). Temporal dependency of survival responses was determined by reseeding cells from the inand outof-field regions at different time post after irradiation. Differential mechanisms of cellular radiobiological response following exposure to intensity-modulated radiation fields