THE RADIOPROTECTIVE EFFECT OF BBI IS ASSOCIATED WITH THE ACTIVATION OF DNA REPAIR-RELEVANT GENES

Purpose: To investigate the molecular mechanisms of the radioprotectiv e effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF). Material and methods: The effect of BBI pre-t reatment on p53 protein level and on mRNA levels of downstream genes ( ERCC3, Gadd45 and p53) was investigated. Results: As indicated by rime -course experiments based on clonogenic assays, a 6 h pre-incubation w ith BBI before irradiation of HSF with a single dose of 6 Gy resulted in maximum radioprotection. In non-irradiated cells, pre-incubation wi th BBI resulted in an increased level of p53 protein. Concomitantly, e nhanced mRNA levels of the ERCC3 and the Gadd45 genes were observed. A s a consequence, BBI-treated cells showed accelerated DNA repair compa red with untreated cells when irradiated. Conclusions: The radioprotec tive effect of the Bowman-Birk proteinase inhibitor was accompanied by elevated mRNA expression of repair-relevant genes prior to irradiatio n. Activation of the DNA-repair machinery induced by pre-treatment wit h BBI is one possible mechanism of the radioprotective effect of BBI.