Conclusions
ROD was greatly augmented by some intracellular reducing agents but others (eg, ascorbate) effectively reversed this effect. Ascorbate had its greatest effect at low oxygen concentrations. ROD decreased with increasing dose rate in most cases.
Purpose
FLASH (dose rates >40 Gy/s) radiation therapy protects normal tissues from radiation damage, compared with conventional radiation therapy (∼Gy/m). Radiation-chemical oxygen depletion (ROD) occurs when oxygen reacts with radiation-induced free radicals, so a possible mechanism for FLASH involves radioprotection by the decreased oxygen as ROD occurs. High ROD rates would favor this mechanism, but prior studies have reported low ROD values (∼0.35 µM/Gy) in chemical environments such as water and protein/nutrient solutions. We proposed that intracellular ROD might be much larger, possibly promoted by its strongly reducing chemical environment.
Results
Reducing agents significantly altered ROD values. Most greatly increased ROD but some (eg, ascorbate) actually decreased ROD and additionally imposed an oxygen dependence of ROD at low oxygen concentrations. The highest values of ROD were found at low dose rates, but these montonically decreased with increasing dose rate. Conclusions: ROD was greatly augmented by some intracellular reducing agents but others (eg, ascorbate) effectively reversed this effect. Ascorbate had its greatest effect at low oxygen concentrations. ROD decreased with increasing dose rate in most cases.