PURPOSE: To investigate the molecular mechanisms of the radioprotective effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF). MATERIAL AND 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.
PURPOSE: To investigate the molecular mechanisms of the radioprotective effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF). MATERIAL AND 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.