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Title: Late radiation morbidity : incidence in a south-east Scottish cohort and investigation into abnormalities in DNA double-strand break repair and damage response
Author: Loong, Susan Li E. R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Late normal tissue injury is dose-limiting for radiation therapy of cancer. The molecular mechanisms of this injury are unknown. However, almost all radiosensitive animals and cell lines are deficient in some aspect of DNA repair. We have derived EBV-transformed cell lines from five patients with late radiation injury to determine whether there was any evidence of reduced activity or expression of the enzymes active in non-homologous recombination, the major mammalian repair pathway for DNA double-strand breaks which cause radiation-induced cell death. Two of these cell lines exhibit post-radiation viability intermediate between normal controls and a cell line from an individual with ataxia-telangiectasia. DNA-dependent protein kinase activity in vitro was reduced 8-10- fold in these two cell lines compared to normal controls. The primary tumours from one of these patients, and a post-radiation cervix biopsy form the second, exhibited no immunoreactivity with a polyclonal antibody against the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). Immunoblotting showed normal levels of Ku70, Ku80 and XRCC4, and the presence of DNA-PKcs, in both cell lines. This suggests that the DNA-dependent protein kinase might be an important factor in determining the predisposition of radiotherapy patients to late radiation injury.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available