Microenvironmental and genetic factors in haemopoietic radiation responses

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced chromosomal instability, bystander effects, the influence of the microenvironment and genetic factors.

Blood cells are continuously produced by the proliferation and differentiation of lineage-specific precursor cells that, in turn, are all derived from a small population of multipotential stem cells. The homeostatic regulation of this hemopoietic hierarchy involves multiple regulatory factors and interactions with the tissue microenvironment and responses of the hemopoietic system are major determinants of outcome after exposure to ionizing radiation. A sub-optimal or aberrant response to radiation-induced damage may divert the system away from effective restoration of tissue homeostasis into responses that ultimately result in pathological changes. DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes is conventionally regarded as the reason for the adverse consequences of radiation exposures. However, reports of radiation-induced genomic instability and radiation-induced bystander effects challenge this conventional paradigm. In the context of the haemopoietic system, these, so called, non-targeted effects can be inter-related 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.