Abstract
Although radiation induced non-targeted response has been well documented in a variety of in vitro and in vivo biological systems, the mechanism is not known. Since mitochondria are the main source of energy production as well as generators of free radicals in cells, the role of mitochondrial function in mediating the non-targeted response in mammalian cells was examined. A microbeam was used to lethally irradiate either mitochondrial DNA depleted (ρo) or wild type (ρ+) human skin fibroblasts with 20 alpha particles each in a mixed, confluent culture, and the bystander response was determined in the non-irradiated fraction. ρ0 cells, when compared with ρ+ cells, showed a higher bystander HPRT- mutagenic response in confluent monolayer when 10% of the same population was lethally irradiated. However, using mixed cultures of ρ0 and ρ+ cells and targeting only one population of cells with a lethal dose of alpha particles, a decreased bystander mutagenesis was uniformly found with both cell types indicating that mitochondrial deficient cells cannot effectively communicate the bystander signals to wild type cells; or alternatively, signals from one cell type can modulate expression of the bystander response in another cell type. These data suggest that mitochondrial signaling pathways are involved in mediating the non-targeted response and a better understanding of the process will allow us to formulate a more accurate model in assessing the health effects of low doses of ionizing radiation.
