INACTIVATION OF P53 IS ASSOCIATED WITH DECREASED LEVELS OF RADIATION-INDUCED APOPTOSIS IN MEDULLOBLASTOMA CELL-LINES

Radiation is the primary therapeutic modality for children with medull oblastoma, a pediatric brain tumour. We examined the response of four medulloblastoma cell lines to ionising radiation. Our evaluation utili sing flaw cytometry, morphological analysis and terminal deoxynucleoti dyl transferase assays demonstrated that medulloblastoma cells undergo radiation-induced apoptosis. p53 mediates radiation-induced apoptosis in many cell types, and p53 mutations have been associated with incre ased resistance to ionising radiation. p53 mutations are rare in medul loblastoma. We found that wildtype p53 is required for high levels of apoptosis in medulloblastoma, and cell lines in which p53 had been ina ctivated by mutation had very low levels of apoptosis. Inactivation of endogenous wildtype p53 in medulloblastoma cells by introduction of a dominant negative mutant of p53 decreased the level of radiation-indu ced apoptosis. Our results suggest that the sensitivity of medulloblas toma to irradiation involves p53-mediated apoptosis and that p53 gene status may be a predictor of response to radiation therapy.