LOW DOSE-RATE FIBROBLAST RADIOSENSITIVITY AND THE PREDICTION OF PATIENT RESPONSE TO RADIOTHERAPY

The relationship between cellular radiosensitivity and normal-tissue r esponse to radiotherapy in individual cancer patients has attracted in creasing attention over the last few years. Recent work has suggested that a correlation exists between fibroblast sensitivity and normal-ti ssue reactions. We have examined the radiosensitivity of fibroblasts g rown from skin biopsies of four normal individuals and three patients identified as having suffered unexpectedly severe reactions to clinica l radiotherapy, called here 'over-reactor' (OR) patients. Clonogenic s urvival was measured after high (HDR) and low dose-rate (LDR) irradiat ion. By comparing the two, an LDR Recovery Factor was derived. Potenti ally-lethal damage repair was examined in 4 cell strains. After HDR th e OR strains were indistinguishable from the normals. At LDR the range of sensitivity was expanded. The OR strains fell at the sensitive end of the range and were characterized by a lack of LDR recovery, which clearly distinguished them from the normal strains. Experimental error s were estimated by considering all the data sets together rather than viewing each experiment individually. Duplicate strains from several patients were tested, and the differences between them were found to b e within the estimated experimental errors, suggesting that these diff erences were not biologically significant. The data are consistent wit h the hypothesis that normal-tissue response is linked to individual c ellular radiosensitivity. Our data confirm the importance of using LDR irradiation in clinical investigations of cellular sensitivity.