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Mechanisms and Genetics of Radiation-Induced Tumorigenesis Mouse Models of Leukaemia, Lymphoma and Skin Neoplasia (MAGELLANS)

Project ID: FIGH-CT-1999-00006
Funded under: FP5-EAECTP C


The development of judgements on post-irradiation cancer risk for the purposes of radiological protection is a complex process which involves evaluation of data on cancer rates in irradiated humans (epidemiology), together with information from animal studies and from investigation of the mechanisms/genetics of cancer induction.
The central estimates of radiation cancer risk are derived from epidemiological studies and these allow for the estimation of cancer risk down to doses of around 100-200 mSv (i.e. a little above the life-time dose from natural background radiation). Since epidemiology does not have the power to directly address cancer risk at the low doses of principal importance in radiological protection, scientifically informed judgements have to be made on the shape of the dose-response for cancer induction. The majority scientific view is that there is a simple proportionate relationship between dose and risk but there are proposals that at low doses there is a dose interval (a dose threshold) where there is no excess risk of cancer.
Much of the information that supports a non-threshold type dose-response comes from fundamental understanding of the manner in which the primary cellular target, DNA, is damaged by radiation and the repair processes that act on that damage. Such repair is judged to be subject to some errors and even at low doses there will be induction of rare cancer-associated mutations in critical genes.
Since radiation-associated human tumours are of very limited availability, research in this whole area is beginning to utilise the increasing power of experimental models of human cancer in mice. The MAGELLANS consortium has used mouse models of acute myeloid leukaemia (AML), lymphoma and skin cancer (with other tumours) to seek further evidence on the mechanisms and genetics of radiation tumorigenesis. This work was conducted under three workpackages (WPs).

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