Irradiation of Mammalian Cells in the Presence of Diamide and Low Concentrations of Oxygen at Conventional and at Ultrahigh Dose Rates

The response of cultured CHO cells to ultrahigh-dose-rate radiation ($\sim 10^{9}\ {\rm Gy}/{\rm sec}$) has been previously studied extensively using the thin-layer cell-handling technique developed in this laboratory. When the cells are equilibrated with a low concentration of oxygen, e.g., 0.44% O2, a breaking survival curve, due to radiolytic depletion of the oxygen, is observed. Hypoxic cells irradiated in the presence of the nitroimidazoles (e.g., misonidazole) are sensitized at ultrahigh dose rates in a dose-modifying manner, similar to that observed at conventional dose rates. These radiosensitizer compounds, if present in cells equilibrated with a low concentration of oxygen, prevent the breaking behavior of the survival curve, an observation believed to be due to the sensitizer interfering with the oxygen depletion process, leaving oxygen free to sensitize. Such experiments have recently been extended to studies with diamide, which, unlike the other sensitizers tested, acts primarily as a shoulder-modifying rather than a dose-modifying agent in hypoxic mammalian cells. These data indicate that diamide is active as a sensitizer at ultrahigh dose rates in a manner similar to that observed at conventional dose rates, and does modify the shape of the breaking survival curve observed with low concentrations of oxygen.