Biological Ageing Effect of Radiotherapy in Breast Cancer

The ability of peripheral blood lymphocytes to undergo radiation-induced apoptosis in vitro usually falls by only 0.5% per year. In a recent study, it has been found that in vitro apoptotic response to ionising radiation in peripheral blood lymphocytes fell by 15% in 12 breast cancer patients when repeated one year post radiotherapy (Docherty et al, 2007). This is equivalent to 30 years of biological ageing over a one year period post irradiation. Our hypothesis is that the decrease in peripheral blood lymphocytes ability to undergo apoptosis is a result of irradiation-induced biological ageing. This project aims to validate proposed in vitro markers of biological ageing in peripheral blood lymphocytes (including global genomic Methylation by High Performance Liquid Chromatography analysis and Telomere Lengths using Single Telomere Length Analysis and Telomere Restriction Fragment analysis) and radiosensitivity assays (including radiation-induced apoptotic response via Sub-G1 and Annexin V/FITC assays, and DNA Single Strand Break & Double Strand Break formation and repair via Comet and gamma-H2AX assays). We plan to investigate these observations within a larger breast cancer patient and control cohort to investigate the cause of biological ageing. It is hoped that these assays could be used to predict response to treatment/complications or prognosis, or to determine the effectiveness of bio-preventative agents in the future.