Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice

The mechanisms by which the p53 tumour suppressor protein would, in vivo, c o-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis, To get further i nsight into the tissue-specific regulation of p53 transcriptional activity, we performed an extensive study looking at the expression of four well cha racterized p53-responsive genes, before and after gamma-irradiation in p53 wild-type (p53 + / +) and p53-deficient (p53 - / -) mice. The waf1, bax, fa s and mdm2 genes were chosen for their different potential roles in the cel lular response to stress. Our data demonstrate the strict p53-dependence of mRNA up-regulation for bar, fas and mdm2 in irradiated tissues and confirm such findings for wafl. They further highlight complex levels of regulator y mechanisms that could lead, in vivo, to selective transcriptional activat ion of genes by p53, In addition, our results provide arguments for the inv olvement of p53 in the basal mRNA expression of the four genes in some orga ns, Finally, in situ expression of Bar and p21Waf-1 protein suggests, at le ast in lymphoid organs, a direct correlation between selective p53-target g ene expression and particular response of a cell to ionising radiation.