SURVIVAL OF SYNCHRONIZED HUMAN NHIK-3025 CELLS IRRADIATED AEROBICALLYFOLLOWING A PROLONGED TREATMENT WITH EXTREMELY HYPOXIC CONDITIONS

Purpose: To investigate whether radiation survival of cells irradiated aerobically in the oxygen-sensitive restriction point in late G1 is d ependent on where in the cell cycle the cells first were rendered hypo xic. Materials and methods: Human cer ix carcinoma, NHIK 3025 cells, w ere synchronized and rendered hypoxic while in early-, mid- or late G1 or in early G2. Cell-cycle progression during the treatment was monit ored by flow cytometry, and cell survival following either hypoxia alo ne or hypoxia with subsequent reoxygenation and irradiation was measur ed 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 initialed DNA synthesis following reoxygenation and irradiation severa l hours later than cells rendered hypoxic in G1. Radiation survival of cells accumulated in the oxygen-sensitive restriction point was indep endent of where in the cell cycle the cells first were rendered hypoxi c. The hypoxia-treated cells had lower radiation survival probability than untreated cells in late G1. Conclusions: Although cells accumulat ed in the oxygen-sensitive restriction point from different parts of t he cell cycle are not biologically identical, they are radiobiological ly similar. The radiosensitizing effect of prolonged hypoxia was not m erely due to cell-cycle redistribution.