RELATIONSHIP BETWEEN RADIATION RESPONSE AND P53 STATUS IN HUMAN BLADDER-CANCER CELLS

Mutations in the p53 tumour suppressor gene are found al high frequenc y in bladder cancer. There is strong evidence that p53 plays an import ant role in controlling the cell cycle after DNA damage by ionizing ra diation. However, the effect of loss of p53 function on radiosensitivi ty is not yet clear. Radiotherapy combined with chemotherapy is the mo st common treatment for patients with invasive bladder cancer. Recentl y three bladder cancer cell lines have been established and this paper investigates the p53 status and clonogenic survival of these cell lin es following irradiation. It was found that one line expresses wt p53 (UCRU-BL-13) and two lines contain a codon 72 polymorphism (UCRU-BL-17 and UCRU-BL-28). UCRU-BL-17 cells also contain a point mutation affec ting codon 280. The level of p53 expression in the cell lines is clear ly different, with UCRU-BL-17 expressing a higher level of p53 compare d with UCRU-BL-13; UCRU-BL-28 expressed intermediate levels. The clono genic survival of these cell lines has been determined. It was found t hat the Line expressing a p53 mutation was more sensitive than those w ith wild type p53, providing support for a model in which loss of p53 function is associated with increased radiosensitivity, possibly due t o reduced p53-dependent DNA repair.