Effects of exposure to low-dose-rate (60)co gamma rays on human tumor cells in vitro

Cells of three asynchronously growing human tumor cell lines, PC3 (human prostate carcinoma), T98G and A7 (human glioblastomas), which have been shown previously to demonstrate low-dose hyper-radiosensitivity to low acute single doses, were irradiated with (60)Co gamma rays at low dose rates (2 cGy-1 Gy h(-1)). Instead of a dose-rate sparing response, these cell lines demonstrated an inverse dose-rate effect on cell survival at dose rates below 1 Gy h(-1), whereby a decrease in dose rate resulted in an increase in cell killing per unit dose. A hyper-radiosensitivity-negative cell line, U373MG, did not demonstrate an inverse dose-rate effect. Analysis of the cell cycle indicated that this inverse dose-rate effect was not due to accumulation of cells in G(2)/M phase or to other cell cycle perturbations. T98G cells in reversible G(1)-phase arrest also showed an inverse dose-rate effect at dose rates below 30 cGy h(-1) but a sparing effect as the dose rate was reduced from 60 to 30 cGy h(-1). We conclude that this inverse dose-rate effect in continuous exposures reflects the hyper-radiosensitivity seen in the same cell lines in response to very small acute single doses.