|Ionizing radiation (IR) is a known human carcinogen. However, the precise molecular mechanisms by which IR induces cancer are very poorly understood. Recent major advances in generating immortal, but otherwise normal cell lines from a variety of specialized human tissues has now made possible the study of the genetics of stages in the development of IR-induced malignancy, using clinically relevant cell system. In this project, these techniques will be combined with advanced molecular cytogenetic methods and proven genetic complementation (i.e. functional) approaches to identify, map and isolate novel genes involved in the process of IR carcinogenesis. Human radiation-associated thyroid cancer cells will be investigated in parallel to in vitro generated tumour cells. A detailed molecular description of chronomosal instability mechanism driving IR-induced malignant development will also be provided.