Oxygen Radiosensitisation at Low Dose Rate

Abstract

Oxygen radiosensitization has been studied at dose rates of 600, 3.37 and 0.89 Gy [grays]/h at pO2 [oxygen partial pressure] levels of 0.001, 0.03, 0.1, 0.3, 1, 3, 10 and 21% in the gas phase. The oxygen enhancement ratio (OER), evaluated at 2% cellular survival, exhibited a decrease with dose rate from a value of 3.2 at the acute dose rate, to 2.4 at the lowest dose rate. This observation results from a decreased dose-rate effect on hypoxic cells, which is attributed to the partial suppression of sublethal damage (SLD) repair under hypoxic conditions. Oxygen radiosensitization at the acute dose rate agrees with the calculated values based on the oxygen fixation hypothesis. Direct application of the Howard-Flanders and Moore equation to results obtained at low dose rate is not appropriate due to the influence of pO2 on SLD repair which affects radiosensitivity at low dose rate. When cells are irradiated at 3.37 Gy/h under nutrient-deprived condition, (i.e., in Hanks balanced salt solution without glucose), low levels of oxygen appear to be more radioprotective than extreme hypoxia. Specifically, cells irradiated with 0.03% and 0.1% O2 are more radioresistant than cells under N2, with enhancement factors of 0.7 and 0.8, respectively. This phenomenon can be understood in terms of the ability of moderately hypoxic cells (0.03%-0.1% O2), and inability of anoxic cells, to repair SLD under nutrient deprived conditions. Radiosensitization by these low levels of oxygen is insufficient to offset the difference caused by the disparate SLD repair capabilities.