The Intrinsic Radiosensitivity of Some Human Tumor Cells Throughout Their Cell Cycles

Abstract

The intrinsic radiosensitivity of tumor cells is most frequently reported for asynchronous populations, although cell cycle variation in radiosensitivity is known to be significant. Linear-quadratic analyses of survival data for asynchronous human tumor cells show wide variations in the alpha coefficient with smaller variations in the beta coefficient. HT-29 (colon), OVCAR10 (ovary) and A2780 (ovary) tumor cells with alpha coefficients of 0.03, 0.16 and 0.47 Gy(-1), respectively, and square-root of beta coefficients of 0.23-0.27 Gy(-1) for asynchronous populations were amenable to synchronization by mitotic selection. Selection procedures were optimized for each cell line and produced mitotic populations of >90%, approximately 80% and approximately 65% purity for HT-29, OVCAR10 and A2780 cells, respectively. Mitotic cells from each line exhibited similar and maximum radiosensitivities with alpha coefficients of approximately 1.3 Gy(-1) after irradiation with 137Cs gamma rays and after correction for genome multiplicity. Their relative radiosensitivities observed with asynchronous cells were maintained as they progressed through interphase of the cell cycle. All cells in early G1 phase exhibited a marked radioresistance relative to their sensitivity in mitosis, and maximum interphase radiosensitivity was observed near the G1/S-phase boundary. All cells became increasingly radioresistant as they moved through S phase, the effect being most pronounced for OVCAR10 cells and least pronounced for A2780 cells. HT-29 cells remained relatively radioresistant in G2 phase. The different interphase radiosensitivities observed for these cell lines were determined mainly by the single-hit inactivation mechanism. These studies clearly demonstrate the dominant role of single-hit inactivation in determining the intrinsic radiosensitivity of human tumor cells to 137Cs gamma rays, especially at doses of 2 Gy and less.