THE SURVIVAL OF ASYNCHRONOUS V79 CELLS AT LOW RADIATION-DOSES - MODELING THE RESPONSE OF MIXED CELL-POPULATIONS

We have observed that when a single linear-quadratic (LQ) function is used to fit the radiation survival response of an asynchronously divid ing population of V79 cells, a consistent misfit occurs at low doses. The data can be better described by fitting the low-dose and high-dose ranges separately, and there is evidence of a two-component response. The most obvious explanation is that we may simply be seeing the resp onse of subpopulations of cells of different radiosensitivity: sensiti ve G(1)-, G(2)- and M-phase cells and resistant S-phase cells. The cel l sorting assay far cell survival which we have used in these studies may thus be providing sufficient accuracy to resolve these subpopulati ons, not previously seen in conventional survival measurements. An alt ernative explanation is that the linear-quadratic function may be inap propriate for accurate description of the radiation survival response at low dose, at least for these cells. To test this hypothesis we have used three other models to fit the data: the single-hit plus multi-ta rget (SHMT) model and the two-parameter repair-misrepair (RMR) model b oth yielded inferior fits to the asynchronous survival data; the three -parameter RMR model provided an improved fit to the data. The best fi t, however, was obtained using a two-population LQ model, which sugges ted approximately equal numbers of sensitive and resistant cells. When the survival response of tightly synchronized G(1)/S-phase cells was measured using the cell sorting assay, no substructure was observed. T his offers strong support to the hypothesis that the substructure obse rved in the asynchronous survival response is due to subpopulations of cells of different, cycle-dependent radiosensitivity.