Prediction of Human Tumour Cell Radiosensitivity as Measured by Radiation-Induced Chromosome Aberrations

摘要

An important goal of current research in radiation oncology is the development of an assay or a combination of assays to predict the radiation response of individual human tumours and normal tissue response. Three important radiobiological parameters have been considered to have a significant effect on a tumour's response to radiotherapy, i.e. intrinsic radiosensitivity, hypoxia and proliferation. All of these parameters will determine the response of the tumour to radiotherapy. In addition, these parameters will provide the clinician not only with the basis for selecting between different treatments but also to provide a more rational way to select patients for appropriate trials and new treatment modalities. In several studies, intrinsic radiosensitivity as determined with a colony assay has been tested as a predictor of treatment outcome. The routine use of a colony assay as a predictive assay is far from optimal, however, since this assay takes several weeks to complete, which is usually unacceptably long for patients waiting for appropriate treatment. Other assays should therefore be developed which can be used routinely in a clinical setting. Any such assay should give a direct or indirect measure of cell killing. Based on the close relationship between radiation-induced chromosome aberrations and cell killing, using conventional techniques, we and others proposed the use of fluorescence in situ hybridisation (FISH) using, chromosome-specific DNA probes for the measurement of radiation-induced chromosome aberrations as a predictor of radiosensitivity. All of the studies using FISH for the detection of radiation-induced chromosome aberrations showed a good correlation between chromosome aberration and cell killing but were performed using a limited number of cell lines. There is only one study which analysed cells of up to seven human tumour cell lines from different sites including breast, lung, and head and neck carcinomas. Other studies tested only two or three human tumour cell lines In the present study, we have further validated the relationship between radiation-induced chromosome aberrations as determined with FISH and cell killing as determined with a colony assay. In addition, we tested a method to separate tumour cells from normal cells and the induction of prematurely condensed chromosomes in fresh tumour tissue after short-term culture.