In the present study we have demonstrated that the Boman-Birk proteinase inhibitor (BBI) protected normal fibroblasts from a radiation-induced 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 TP53 (formerly known as p53) in normal fibroblasts. In transformed fibroblasts, BBI failed to induce these effects. The analysis of the TP53 gene in transformed fibroblasts revealed a mutation in exon 5. As a consequence of this mutation, the expression of the TP53 downstream gene CDKN1A (p21/WAF1/Cip1) is blocked. Based on experiments using TP53 antisense oligonucleotides, the radioprotective effect of BBI could be correlated with the function of wild-type TP53. Thus BBI can be considered as a selective radioprotective agent for normal human fibroblasts.
The Presence of Wild-Type TP53 Is Necessary for the Radioprotective Effect of the Bowman-Birk Proteinase Inhibitor in Normal Fibroblasts
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Klaus H. Dittmann, Nuri Gueven, Claus Mayer, Petra Ohneseit, Roland Zell, Adrian C. Begg, H. Peter Rodemann; The Presence of Wild-Type TP53 Is Necessary for the Radioprotective Effect of the Bowman-Birk Proteinase Inhibitor in Normal Fibroblasts. Radiat Res 1 December 1998; 150 (6): 648–655. doi: https://doi.org/10.2307/3579887
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