CHARACTERIZATION OF THE G1 S CELL-CYCLE CHECKPOINT DEFECT IN LUNG-CARCINOMA CELLS WITH DIFFERENT INTRINSIC RADIOSENSITIVITIES/

Cell cycle perturbations in three lung carcinoma cell lines (U-1285,U1 906 and U-1820) with different intrinsic radiosensitivities (SF2 (U-12 85)= 0.25, SF2 (U-1906)= 0.45, SF2 (U-1810)= 0.88) were investigated f ollowing x-irradiation. Cell cycle flow calculations showed that the G 1 --> S-phase transit was accelerated in irradiated compared with untr eated U-1285 cells, up to 24 hours postirradiation. In U-1810 cells an d U-1906 cells the postirradiation GI --> S transit decreased compared with controls. All three cell lines showed no postirradiation inducti on of p53 and p21(CIP1) proteins. Cyclin E was overexpressed and cycli n E-dependent kinase activity was substantially induced by irradiation in U-1285 cells compared with U-1906 and U1810 cells while p27(KIP1) was detected at the highest intensity in U1810 cells and lowest in U-1 285 cells. We hypothesise that the accelerated postirradiation G1-->S transit in U-1285 cells is associated with induction of cyclin E-depen dent kinase activity and may account for increased radiosensitivity in these cells.