%0 Journal Article
%T A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose
%A Anthony J Chalmers
%A Soeren M Bentzen
%A Francesca M Buffa
%J Theoretical Biology and Medical Modelling
%D 2007
%I BioMed Central
%R 10.1186/1742-4682-4-25
%X An indicator model that allowed quantification of the Sensitiser Effect on Radiation response as a function of Dose (SERD) was developed. This model was fitted to clonogenic survival data derived from human tumour and rodent fibroblast cell lines irradiated in the presence and absence of chemical inhibitors of poly(ADP-ribose) polymerase (PARP) activity.PARP inhibition affected radiation response in a cell cycle and radiation dose dependent manner, and was also associated with significant radiation-independent effects on clonogenic survival. Application of the SERD method enabled identification of components of the radiation response that were significantly affected by PARP inhibition and indicated the magnitude of the effects on each component.The proposed approach improves on current methods of analysing effects of DNA repair modification on radiation response. Furthermore, it may be generalised to account for other parameters such as proliferation or dose rate to enable its use in the context of fractionated or continuous radiation exposures.Radiotherapy is an effective mode of cancer treatment but its capacity to cure is limited by toxic effects on healthy tissues. Developing effective treatment schedules requires detailed knowledge of the cellular effects of radiation in tumours and normal tissues so that differences may be exploited and a beneficial therapeutic ratio achieved. Increasing evidence indicates that DNA repair pathways are a key determinant of cell survival after radiation, and that targeting the molecular components of these pathways offers therapeutic potential [1-3].When assessing the impact of modifiers of DNA repair on cellular responses to ionising radiation, accurate measurement of effects on clonogenic survival is crucial, since this is the most clinically relevant radiation response [4]. Data are generally presented in the form of survival curves, which illustrate radiation effects over a range of doses and may be described by parameters t
%U http://www.tbiomed.com/content/4/1/25