Role of wild-type p53 in apoptotic and non-apoptotic cell death induced by X-irradiation and heat treatment in p53-mutated mouse m10 cells

The sensitizing effects of wild-type p53 on x-ray-induced cell death and on heat-induced apoptosis in m10,a radiosensitive and trp53 (mouse p53 gene)-mutated lymphoma cell line which dies through necrosis by x-irradiation,were investigated using three m10 derived transfectants with wild-type tp53(human p53 gene). cell death was determined by colony formation and/or dye exclusion test,and apoptosis was detected as the changes in nuclear morphology by giemsa staining. expression of wild-type p53 protein increased radiosensitivity of cell death as determined by both clonogenic and dye exclusion assays. this increase in radiosensitivity was attributable largely to apoptosis induction in addition to a small enhancement of necrosis. interestingly neither pathway to cell death was accompanied by caspase-3 activation. on the other hand,heat-induced caspase-3 dependent apoptotic cell death without transfection was further increased by the transfection of wild-type p53. in conclusion,the introduction of wild-type p53 enhanced apoptotic cell death by x-rays or heat via different mechanisms that do or do not activate caspase-3,respectively. in addition,p53 also enhanced the x-ray-induced necrosis in m10 cells.