THE PRESENCE OF WILD-TYPE TP53 IS NECESSARY FOR THE RADIOPROTECTIVE EFFECT OF THE BOWMAN-BIRK PROTEINASE-INHIBITOR IN NORMAL FIBROBLASTS

In the present study we have demonstrated that the Bowman-Birk protein ase inhibitor (BBI) protected normal fibroblasts from a radiation-indu ced reduction in cell survival, whereas in transformed fibroblasts no radioprotective effect was observed. It was shown that BBI reduced the radiation-induced protein stabilization and DNA-binding activity of T P53 (formerly known as p53) in normal fibroblasts, In transformed fibr oblasts, BBI failed to induce these effects. The analysis of the TP53 gene in transformed fibroblasts revealed a mutation in exon 5, As a co nsequence of this mutation, the expression of the TP53 downstream gene CDKN1A (p21/WAF1/Cip1) is blocked. Based on experiments using TP53 an tisense oligonucleotides, the radioprotective effect of BBI could be c orrelated with the function of wild-type TP53, Thus BBI can be conside red as a selective radioprotective agent for normal human fibroblasts, (C) 1998 by Radiation Research Society.