Response of sensitive human ataxia and resistant T-1 cell lines to accelerated heavy ions.
We have studied the radiation dose responses of two human fibroblast lines: cells from a patient with Ataxia telangiectasia (AT-2SF) and an established line of human T-1 cells. Aerobic and hypoxic 225 kVp X-ray survival curves were used as controls to the heavy ion exposures. Nearly monoenergetic accelerated neon and argon ions were used at the Berkeley Bevalac with various residual range values. The LET of the particles varied from 30 keV microns-1 to over 1,000 keV microns-1. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100-200 keV microns-1. Human T-1 cells have effective sublethal damage repair as has been evidenced by split dose experiments, and they are much more resistant to low LET than to high LET radiation. At high LET their radiosensitivity approached that of the Ataxia cells. The repair-misrepair model has been used to interpret these results. According to this model, the molecular repair processes culminate either in eurepair or in misrepair. We have obtained mathematical expressions that describe the cross sections and inactivation coefficients for both human cell lines as a function of the LET and the type of particle used. We assume that the lesions induced in T-1 and Ataxia cells are qualitatively similar and that each cell line attempts to repair these lesions. The result in most irradiated Ataxia cells, however, is either lethal misrepair or incomplete repair leading to cell death. T-1 cells have efficient repair mechanisms at low LET, and the repair-misrepair model suggests that at high LET the T-1 cells can still efficiently repair individual lesions, but that as the lesions become closely spaced along the tracks, the probability of misrepair increases.
D001260:Ataxia Telangiectasia / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004735:Energy Transfer; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D007668:Kidney; D008954:Models, Biological; D010100:Oxygen; D012062:Relative Biological Effectiveness
D010100:Oxygen