THE INTRINSIC RADIOSENSITIVITY OF SOME HUMAN TUMOR-CELLS THROUGHOUT THEIR CELL-CYCLES

The intrinsic radiosensitivity of tumor cells is most frequently repor ted for asynchronous populations, although cell cycle variation in rad iosensitivity is known to be significant. Linear-quadratic analyses of survival data for asynchronous human tumor cells show wide variations in the cw coefficient with smaller variations in the beta coefficient . HT-29 (colon), OVCAR10 (ovary) and A2780 (ovary) tumor cells with al pha coefficients of 0.03, 0.16 and 0.47 Gy(-1), respectively, and root beta coefficients of 0.23-0.27 Gy(-1) for asynchronous populations we re amenable to synchronization by mitotic selection. Selection procedu res were optimized for each cell line and produced mitotic populations of >90%, similar to 80% and similar to 65% purity for HT-29, OVCAR10 and A2780 cells, respectively. Mitotic cells from each line exhibited similar and maximum radiosensitivities with alpha coefficients of simi lar to 1.3 Gy(-1) after irradiation with Cs-137 gamma rays and after c orrection for genome multiplicity. Their relative radiosensitivities o bserved with asynchronous cells were maintained as they progressed thr ough interphase of the cell cycle. All cells in early G(1) phase exhib ited a marked radioresistance relative to their sensitivity in mitosis , and maximum interphase radiosensitivity was observed near the G(1)/S -phase boundary. All cells became increasingly radioresistant as they moved through S phase, the effect being most pronounced for OVCAR10 ce lls and least pronounced for A2780 cells. HT-29 cells remained relativ ely radioresistant in G(2) phase. The different interphase radiosensit ivities observed for these cell lines were determined mainly by the si ngle-hit inactivation mechanism. These studies clearly demonstrate the dominant role of single-hit inactivation in determining the intrinsic radiosensitivity of human tumor cells to Cs-137 gamma rays, especiall y at doses of 2 Gy and less. (C) 1997 by Radiation Research Society.