Dittmann K H, Gueven N, Mayer C, Rodemann H P
Department of Radiotherapy, Eberhard-Karls-University, Tübingen, Germany.
Int J Radiat Biol. 1998 Aug;74(2):225-30. doi: 10.1080/095530098141609.
To investigate the molecular mechanisms of the radioprotective effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF).
The effect of BBI pre-treatment on p53 protein level and on mRNA levels of downstream genes (ERCC3, Gadd45 and p53) was investigated.
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.
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.
研究鲍曼-伯克蛋白酶抑制剂（BBI）对正常人皮肤成纤维细胞（HSF）辐射防护作用的分子机制。
研究BBI预处理对p53蛋白水平以及下游基因（ERCC3、Gadd45和p53）mRNA水平的影响。
基于克隆形成试验的时间进程实验表明，用6 Gy单剂量照射HSF前，先与BBI预孵育6小时可产生最大程度的辐射防护作用。在未受照射的细胞中，与BBI预孵育会导致p53蛋白水平升高。同时，观察到ERCC3和Gadd45基因的mRNA水平增强。因此，与未处理的细胞相比，经BBI处理的细胞在受到照射时显示出更快的DNA修复速度。
鲍曼-伯克蛋白酶抑制剂的辐射防护作用伴随着照射前修复相关基因mRNA表达的升高。BBI预处理诱导的DNA修复机制激活是BBI辐射防护作用的一种可能机制。
