P53 IS REQUIRED FOR RADIATION-INDUCED APOPTOSIS IN MOUSE THYMOCYTES

THE p53 tumour suppressor gene is the most widely mutated gene in huma n tumorigenesis1,2. p53 encodes a transcriptional activator3-7 whose t argets may include genes that regulate genomic stability8,9, the cellu lar response to DNA damage10,11, and cell-cycle progression12-13. Intr oduction of wild-type p53 into cell lines that have lost endogenous p5 3 function can cause growth arrest14-16 or induce a process of cell de ath known as apoptosis17,18. During normal development, self-reactive thymocytes undergo negative selection by apoptosis19, which can also b e induced in immature thymocytes by other stimuli, including exposure to glucocorticoids15 and ionizing radiation16. Although normal negativ e selection involves signalling through the T-cell receptor14, the ind uction of apoptosis by other stimuli is poorly understood. We have inv estigated the requirement for p53 during apoptosis in mouse thymocytes . We report here that immature thymocytes lacking p53 die normally whe n exposed to compounds that may mimic T-cell receptor engagement and t o glucocorticoids but are resistant to the lethal effects of ionizing radiation. These results demonstrate that p53 is required for radiatio n-induced cell death in the thymus but is not necessary for all forms of apoptosis.