The radioprotective effect of BBI is associated with the activation of DNA repair-relevant genes.
OBJECTIVE
To investigate the molecular mechanisms of the radioprotective effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF).


METHODS
The effect of BBI pre-treatment on p53 protein level and on mRNA levels of downstream genes (ERCC3, Gadd45 and p53) was investigated.


RESULTS
As indicated by time-course experiments based on clonogenic assays, a 6 h pre-incubation with BBI before irradiation of HSF with a single dose of 6 Gy resulted in maximum radioprotection. In non-irradiated cells, pre-incubation with BBI resulted in an increased level of p53 protein. Concomitantly, enhanced mRNA levels of the ERCC3 and the Gadd45 genes were observed. As a consequence, BBI-treated cells showed accelerated DNA repair compared with untreated cells when irradiated.


CONCLUSIONS
The radioprotective effect of the Bowman-Birk proteinase inhibitor was accompanied by elevated mRNA expression of repair-relevant genes prior to irradiation. Activation of the DNA-repair machinery induced by pre-treatment with BBI is one possible mechanism of the radioprotective effect of BBI.
Department of Radiotherapy, Eberhard-Karls-University, Tübingen, Germany.
K H
KH
Dittmann
N
N
Gueven
C
C
Mayer
H P
HP
Rodemann
D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D005347:Fibroblasts; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000528:radiation effects; D000097642:GADD45 Proteins
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C078672:hay protein, Drosophila