THE P53 RESPONSE TO IONIZING-RADIATION IN ADULT AND DEVELOPING MURINETISSUES

The induction of the p53 response to ionising radiation has been studi ed during murine development and in the adult animal. The response has been assessed by precise quantitative assay of p53 protein levels in tissues and by immunohistochemistry. Newly developed transgenic mice i n which a lacZ transgene is driven by a p53 response element have also been used to directly assess the transcriptional activity of the indu ced protein, There is striking developmental control of the p53 respon se so that in early development all tissues accumulate high levels of p53 following radiation and indeed p53 is present at elevated levels i n some unirradiated tissues, Later in development clear heterogeneity of the p53 response becomes apparent, both in terms of the responses o f individual tissues and of cell populations, within those tissues, Th e study of lacZ transgene expression and the occurrence of apoptosis i n different tissues that accumulate p53 protein point to a further lev el of control regulating the nature and degree of the downstream respo nse to elevated levels of p53 in cells, These findings have important implications for the susceptibility of different tissue types to carci nogenic and other insults, The early expression of the p53 response is consistent with novel models of p53 function that suggest it may have evolved principally as a defense against teratogenic insult that perm its plasticity of development.