Abstract
In the present study, to investigate the role of mitochondria in the events of radiation induced bystander effects (RIBE), we used either mtDNA-depleted AL or normal AL cells as irradiated donor cells and normal human skin fibroblasts as receptor cells in a series of medium transfer experiments. Our results indicated that mtDNA-depleted cells or normal AL cells treated with the inhibitors for mitochondrial respiratory chain function had an attenuated gamma-H2AX induction in receptor cells. Moreover, it was found that treatment of normal AL donor cells with specific inhibitors of NOS, or inhibitor of mitochondrial calcium uptake (Ruthenium Red), gamma-H2AX induction in receptor cells was significantly decreased and that radiation could stimulate cellular NO and O2.- production in irradiated normal AL cells, but not in mtDNA-depleted AL cells. These observations, together with the findings that Ruthenium Red treatment significantly reduced the NO and O2.- levels in irradiated normal AL cells, suggest that mitochondria play a functional role in RIBE and calcium-dependent mitochondrial NOS might play an essential role in the process.
