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 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.
Dittmann
K H
KH
Department of Radiotherapy, Eberhard-Karls-University, Tübingen, Germany.
Gueven
N
N
Mayer
C
C
Ohneseit
P
P
Zell
R
R
Begg
A C
AC
Rodemann
H P
HP
D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D002461:Cell Line, Transformed; D003114:Colony-Forming Units Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D016158:Genes, p53 / Q000528:radiation effects; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D011837:Radiation-Protective Agents; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D016159:Tumor Suppressor Protein p53; D004247:DNA