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

Abstract

The response of cultured CHO [Chinese hamster ovary] cells to ultrahigh-dose-rate radiation (.apprx. 109 Gy [gray]/s) 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 O2, e.g., 0.44% O2, a breaking survival curve, due to radiolytic depletion of the O2, 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 O2 prevent the breaking behavior of the survival curve, an observation believed to be due to the sensitizer interfering with the O2 deletion process, leaving O2 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. Diamide is apparently 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 O2.