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Mechanisms and genetics of radiation induced tumorigenesis: mouse models of leukaemia, lymphoma and skin neoplasia

Deliverables

At the end of the contract the consortium has published/submitted 27 scientific papers in the open literature that relate to the mechanisms and genetics of radiation tumorigenesis. The position is that these and unpublished data add further support to the importance of a gene loss mechanism for the early action of radiation in multi-stage tumorigenesis in the skin and haemopoietic system. Coupled with other knowledge, this developing biological concept may be used to argue against a low dose threshold for tumour risk. Although less well developed, the genetic studies on tumour susceptibility have succeeded in identifying several candidate genes (Pthlh and Scaa2 for skin; Prkdc in the breast and intestine. For leukaemia there is evidence of a novel genetic association between the expression of chromosomal fragile sites and modified chromatin re-modelling. By coupling these data with other knowledge it is possible to project the multiple interaction of genetic determinants of risk with different tumour types usually being influenced by different sets of genes. Overall, recent advances in genomics mean that mouse models of tumorigenesis are increasingly valuable for the provision of proof-of-principle evidence to guide judgements concerning radiological risk and protection within the EU and, internationally, by ICRP and UNSCEAR.