Survival of synchronized human NHIK 3025 cells irradiated aerobically following a prolonged treatment with extremely hypoxic conditions

Abstract

Purpose : To investigate whether radiation survival of cells irradiated aerobically in the oxygen-sensitive restriction point in late G1 is dependent on where in the cell cycle the cells first were rendered hypoxic. Materials and methods : Human cervix carcinoma, NHIK 3025 cells, were synchronized and rendered hypoxic while in early-, midor late G1 or in early G2. Cell-cycle progression during the treatment was monitored by flow cytometry, and cell survival following either hypoxia alone or hypoxia with subsequent reoxygenation and irradiation was measured by the ability of the cells to form macroscopic colonies. Results : During prolonged hypoxia, all surviving cells accumulated in an oxygen-sensitive restriction point in late G1. Cells rendered hypoxic in G2 initiated DNA synthesis following reoxygenation and irradiation several hours later than cells rendered hypoxic in G1. Radiation survival of cells accumulated in the oxygensensitive restriction point was independent of where in the cell cycle the cells first were rendered hypoxic. The hypoxia-treated cells had lower radiation survival probability than untreated cells in late G1. Conclusions : Although cells accumulated in the oxygen-sensitive restriction point from different parts of the cell cycle are not biologically identical, they are radiobiologically similar. The radiosensitizing effect of prolonged hypoxia was not merely due to cell-cycle redistribution.