THE BETA-COMPONENT OF HUMAN CELL-SURVIVAL CURVES AND ITS RELATIONSHIPWITH SPLIT-DOSE RECOVERY

In principle, alpha and beta can be obtained from single-dose survival curves using standard linear-quadratic fitting; however, alpha and be ta being interdependent, it is difficult to evaluate them together wit h good precision. On the assumption that full recovery from a split-do se treatment gives a result that is the product of the single-dose sur viving fraction, it has been suggested that the measurement of split-d ose recovery should provide a method to measure beta alone using the f ormula: beta(RR) = 1nRR/2d(2). Most of the studies published to date h ave been carried out on cancer cell lines or transformed normal cells. We have systematically tested the above proposal on two normal human fibroblast cell lines (HF19 and 1BR3) in two different situations: gro wing cells, and plateau-phase cells. Two different protocols were used to assess both the potential influence of a priming dose on the survi ving cells and the extent of the split-dose recovery. The survival cur ves generated after different priming doses did not show any significa nt change in comparison with those achieved without previous irradiati on. In addition, the split-dose survival was not different from the sq uare of the corresponding single-dose survival (model free). In these conditions, beta(RR)'s obtained by a linear regression of the recovery ratio data were very similar to the beta's obtained by single doses. However, a curvilinear regression (with a very small negative term at high doses) appears to be more appropriate for cells in plateau phase. This has the result that, as the dose increases, the cell survival cu rves tend to become less bending than would be expected from the linea r quadratic model; however, the linear-quadratic fitting is still a re asonable characterization of the radiation response since the in vitro colony formation method does not allow measurement of survival <10(-4 ).