Cell inactivation by combined low dose-rate irradiation and intermittent hypoxia.

PURPOSE: To investigate in detail the earlier observed combined effect of low dose-rate ß-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3-6 weeks. MATERIAL AND METHODS: Continuous low dose-rate ß-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [(3)H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O2 using an INVIVO2 hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments. RESULTS: After 3-6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1-2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O2 at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60-80%. CONCLUSIONS: Treatment of T-47D cells with low dose-rate ß-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.