Oxygen Diffusion into Mammalian Cells Following Ultrahigh Dose Rate Irradiation and Lifetime Estimates of Oxygen-Sensitive Species

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Abstract
Based on the observation of breaking survival curves for cultures [Chinese hamster ovary] CHO cells irradiated by single pulses of high-intensity radiation, the kinetics of O2 diffusion into these cells was studied using the double-pulse technique developed previously with bacterial systems. Two high-intensity electron pulses, each of 3 ns duration, were delivered to a monolayer of CHO cells in equilibrium with a known concentration of O2 (typically .apprx. 0.44% O2). The 1st pulse was of sufficient dose to deplete the intracellular O2 radiochemically and preceded a similar 2nd pulse by an accurately known interpulse time, variable from 10-6 to 60 s. The relative concentration of oxygen diffusing to critical sites in the cell during the interpulse time was inferred by comparing the cellular response to the time-delayed 2nd pulse with that to single pulses under various known O2 concentrations. The O2 diffusion curve obtained experimentally can be described by the solution of a one-dimensional diffusion equation using the O2 diffusion coefficient in water of 2 .times. 10-5 cm2/s and an average depth of the critical sites of 4 .mu.m corresponding approximately to a cell radius. The O2 diffusion curve indicates that a significant amount of O2 diffused to these sites by .apprx. 3 .times. 10-3 s. This can be interpreted as an upper limit to the average life-time of the radiation-induced O2 dependent damage since otherwise breaking survival curves would not have been observed.