Ionizing radiation and secondary leukaemia: experimental approaches

The mechanisms underlying the unequivocal association between ionizing radiation and the development of leukaemia remain unknown. Recent studies present a rather complex picture where, in addition to damage induced directly in target stem cells, a variety of genotype-dependent cellular interactions may also make important contributions to determining overall outcome. The new findings indicate that, contrary to conventional radiobiological models, all adverse effects need not necessarily be induced at the time of irradiation and that indirect effects mediated through the microenvironment may promote pre-existing potentially leukaemic cells as a consequence of genotype-dependent, inflammatory-type responses to radiation-induced tissue injury. Genetic factors also significantly influence the number of irradiated cells that survive with potential to express radiation-induced damage and the genetic background producing the more effective apoptotic response would more effectively eliminate unstable and potentially malignant cells.