Host: The Japan Radiation Research Society
Despite considerable research effort, the mechanisms underlying the unequivocal association between accidental, occupational or therapeutic exposures to ionizing radiation and the development of leukaemia remain unknown. Conventionally, the responsible genetic lesions have been attributed to DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes. However, many reports of, so called, non-(DNA)targeted effects of ionizing radiation in the unirradiated descendants of irradiated cells (radiation-induced genomic instability) or in cells that have communicated with irradiated cells (radiation-induced bystander effects) challenge this conventional paradigm. In the context of the haemopoietic system, the two phenomena are inter-linked and an instability phenotype need not necessarily be a reflection of genomically unstable cells but a reflection of responses to ongoing production of damaging bystander signals in the tissue microenvironment. Both the production of and the response to such signals are influenced by genetic factors and the cell interactions have properties in common with inflammatory mechanisms. Thus, superimposed on damage induced directly in target stem cells, cell interactions make important contributions to determining overall outcome after radiation exposure and have significant implications for the potential health consequences.
