B17
Evaluation of the alkaline comet assay as a predictive test of bladder cancer treatment
Karen Bowman1, Benedict Sherwood3, Alexandra Colquhoun2, Jonathan Goddard2, David Payne2, Sadmeet Singh2, Leyshon Griffiths1, Paul Butterworth2, Masood Khan2, Duncan Summerton2, R. Paul Symonds1, William Steward1, Roger Kockelbergh2, J. Kilian Mellon1, George D. D. Jones1
1Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK, 2Department of Urology, University Hospitals of Leicester NHS Trust, Leicester, UK, 3Department of Urology, King's Mill Hospital, Nottinghamshire, UK
Background
The main treatment options for bladder cancer are radiotherapy (RT) and/or cystectomy for invasive disease and resection plus chemotherapy for non-invasive disease. If the radiosensitivity of invasive tumours could be predicted in advance, it may be possible to significantly improve control rates by selecting for immediate RT those patients with radiosensitive tumours; additionally, those patients with radioresistant tumours (who would benefit from immediate surgery) would be identified earlier, reducing the risk of metastatic spread.
Method
Previously, we’ve shown that induction and repair of DNA single strand breaks (SSBs) as measured by alkaline comet assay (ACA) correlates strongly with cell survival in human bladder cancer cell lines. In this study we further evaluate ACA as a predictive test in the clinical treatment of bladder cancer.
Results and discussion
At clinically relevant doses (2-6 Gy), a dose-dependent increase and time-dependent repair of ex vivo radiation-induced SSBs was observed for each tumour sample; a ~4-fold difference in immediate comet formation and relative ACA response gradient (compared to a control cell line) was observed. These differences may reflect actual differences in tumour cell radiosensitivity. Whilst there is no significant difference between the apparent relative cell radiosensitivities of tumour cells derived from invasive vs. non-invasive disease, high degrees of apparent radio-resistance observed for some invasive samples may be significant in accounting for the current high level of RT treatment failure. Further correlation of ACA measures with tumour outcome after treatment, and ultimately patient survival, will be evident as patient follow-up proceeds.
