Bystander effect of conditioned medium from low and high doses of γ-irradiated human leukemic cells on normal lymphocytes and cancer cells.

The present study investigated the effect of irradiated conditioned medium (ICM), obtained from human promyelocytic leukemic cells (HL-60) γ-irradiated either with low-dose (5 cGy; ICM-L) or high-dose radiation (1 Gy; ICM-H) on unirradiated HL-60 and normal human blood lymphocytes. A dose-dependent increase in apoptosis was observed in HL-60 cells cultured in ICM obtained after different doses of irradiation (0.5-10 cGy), which showed saturation in ICM from 5 cGy. Furthermore, ICM-L and ICM-H induced differential apoptotic responses in unirradiated HL-60 cells and lymphocytes. Apoptosis in lymphocytes cultured in ICM-H was significantly higher than when cells were cultured in unirradiated conditioned medium or ICM-L. Furthermore, induction of apoptosis in bystander HL-60 cells and lymphocytes cultured in ICM-L/ICM-H seems to be associated with an increase in intracellular reactive oxygen species (ROSs) and alterations in mitochondrial membrane potential. These results suggest that differential bystander responses from irradiated cancer cells toward cancer and normal cells depending on the applied dose and/or dose rate of radiation.