학술논문
The Presence of Wild-Type TP53 Is Necessary for the Radioprotective Effect of the Bowman-Birk Proteinase Inhibitor in Normal Fibroblasts
Document Type
research-article
Author
Source
Radiation Research, 1998 Dec 01. 150(6), 648-655.
Subject
Language
English
ISSN
00337587
19385404
19385404
Abstract
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.