Genomic instability and bystander effects: a historical perspective

Data have been emerging over the past two decades concerning two phenomena in which important biological effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. In the first, radiation-induced genomic instability, biological effects occur in the progeny of the irradiated cell after many generations of cell division. In the second, radiation-induced bystander effects, they arise in cells that receive no radiation exposure as a consequence of damage signals transmitted from neighboring irradiated cells; transmission may be mediated either by direct intercellular communication through gap junctions, or by factors released into the surrounding medium. In both phenomena, the biological effects appear to be associated with an upregulation of oxidative metabolism. The present paper is designed to review the historical background leading to our current knowledge of these two phenomena, and to indicate some future directions for research that will allow us to assess better their importance in the health effects of exposure to ionizing radiation.