Modification of radiation sensitivity by edaravone

Studied was the effect of edaravone (E), a clinical therapeutic drug for brain infarction possessing properties of free radical scavenger, on apoptosis in vitro. Human T-cell leukemic MOLT-4 cells and p53-knockdown MOLT-4 cells which overexpressing short hairpin type p53 by siRNA treatment were X-irradiated by Shimadzu Pantak HF 350 machine at 135-140 cGy/min for 2-5 Gy in total, in the presence of E. Cell death was estimated by dye-exclusion, apoptosis by EPICS flow cytometry, cellular reactive oxygen species by chloromethyl-2',7'-dichlorodihydrofluoresein diacetate (CM-H2-DCFDA) fluorometry, and p53-related protein expression by Western blotting. E was found to have a radio-protective effect on cells at high concentrations (e.g., 2.7 and 3 mg/mL, 2Gy) and radio-sensitizing action at low concentrations (e.g., 0.15-1.5 mg/mL). Clinical plasma levels of E have been reportedly far lower than the concentrations in this experiment: ideally, E can sensitize tumor cells to radiation and protect normal cells from. (K.T.)