Interaction of Nitroimidazole Sensitizers and Oxygen in the Radiosensitization of Mammalian Cells at Ultrahigh Dose Rates

Abstract

When CHO [Chinese hamster ovary] cells, equilibrated with 0.44% O2, are irradiated with single 3-ns pulses of electrons from a 600-kV-field emission source, a breaking survival curve is observed. The breaking behavior, believed to be the result of radiolytic O2 depletion, can be prevented by the presence of a relatively low concentration of the hypoxic cell sensitizer misonidazole; similar results are obtained with metronidazole and Ro-05-9963. The resulting survival curves exhibit a sensitized response similar to that obtained with conventional dose rate radiation for CHO cells under this O2 concentration. This degree of sensitization is greater than that observed for CHO cells irradiated at ultrahigh dose rates under the same concentration of sensitizer N2. The nitroimidazole compounds may interfere with the radiation chemical O2 depletion process and the radiosensitization observed in the nonbreaking survival curve is the consequence of sensitization by both the nitroimidazole and, primarily, the O2 rather than a direct substitution for O2 by the sensitizer. This conclusion is also supported by data obtained in double-pulse experiments. The results are discussed with regard to the mechanisms of the O2 depletion process and radiosensitization and in regard to cancer radiotherapy.