Radiosensitivity
In vitro chromosomal radiosensitivity assays measure individual variation in sensitivity to ionising radiation. At Westlakes, we use a technique called the G2 chromosomal radiosensitivity assay in which blood cultures are irradiated using our on-site X-ray facility. Enhanced G2 chromosomal radiosensitivity has been detected in a number of well-defined cancer susceptibility syndromes, most notably ataxia telangiectasia. In addition, elevated chromosomal radiation sensitivity has been demonstrated in peripheral blood lymphocytes from a high proportion of patients with a diverse range of cancers, e.g. breast and colon, leading to suggestions that it could be a marker of cancer predisposing genes.
Recently we have undertaken collaborative work as part of a large-scale retrospective cohort study known as the ‘Genetic Consequences of Cancer Treatment (GCCT) Study’ (http://www.gcct.org/). Through this collaboration, peripheral blood samples have been collected from the Danish families of over 50 survivors of childhood and adolescent cancer and evaluated for their G2 chromosomal radiosensitivity status, enabling us to investigate the links between individual variation in radiosensitivity in relation to cancer predisposition (Curwen et al., 2005). This study has also provided us with a unique opportunity to determine if the cellular response can be inherited in the offspring. Polymorphisms in a panel of DNA damage recognition and repair gene have also been investigated in these individuals for their influence on cancer susceptibility and G2 chromosomal radiosensitivity (Wilding et al., 2007).
The principle aims of these studies are to answer the following questions:
- Do childhood and adolescent cancer survivors exhibit increased G2 chromosomal radiosensitivity in comparison with a control group (their partners)?
- Is the cellular response observed in the cancer survivor inherited in the offspring?
- Are particular polymorphisms in DNA damage recognition and repair genes related to G2 chromosomal radiosensitivity?
Principal Investigator : Dr Gillian Curwen
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