Abstract
Although radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, the mechanism of this phenomenon is not known. The bystander observations have been made with both sub-confluent and confluent cultures as well as in three dimensional tissue cultures in a variety of endpoints. There is evidence that reactive radical species, cytokines and gap junctions are critical in mediating the bystander events. Monoclonal inhibitory antibody against TNF-a substantially suppressed cyclooxygenase 2 (COX-2) expressions in bystander cells via inhibition of the NF-kB pathway. Likewise, Bay 11-7082, a pharmacological inhibitor of NF-kB activation, demonstrated a similar effect in suppressing COX-2 activities and the bystander effects in human fibroblasts. Since COX-2 plays an important role in arachidonic acid metabolism and implicates the involvement of reactive radical species, mitochondrial DNA depleted (rho0) cells were used to illustrate the importance of mitochondrial oxidative metabolism in the bystander process. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell. A better understanding of the cellular and molecular mechanisms of the bystander phenomenon together with evidence of their occurrence in vivo will allow us to formulate a more accurate model in assessing the health effects of low doses of ionizing radiation.
