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  • Title: Bowman-Birk protease inhibitor activates DNA-dependent protein kinase and reduces formation of radiation-induced dicentric chromosomes.
    Author: Dittmann K, Virsik-Köpp P, Mayer C, Rave-Fränk M, Rodemann HP.
    Journal: Int J Radiat Biol; 2003 Oct; 79(10):801-8. PubMed ID: 14630539.
    Abstract:
    PURPOSE: To test a stimulatory effect of the radioprotector Bowman Birk protease inhibitor (BBI) upon DNA repair processes. MATERIALS AND METHODS: An effect of BBI upon DNA repair was investigated by quantification of radiation-induced dicentric chromosomes. Sensitivity to ionizing radiation was determined by clonogenic survival assay. Quantification of activity of the DNA-dependent kinase was performed by immunoprecipitation and phosphorylation of a TP53-derived peptide. RESULTS: The formation of radiation-induced dicentric chromosomes was reduced significantly after pretreatment of cells with BBI. By using a cell line with an inducible expression of a mutated TP53, it was shown that the BBI-mediated reduction of dicentric chromosome formation depended on the presence of wild-type TP53. To get further insights into the molecular mode of action of BBI, activity of the DNA-dependent protein kinase (DNA-PK) was quantified. BBI treatment resulted in a stimulation of basal (DNA-PK) activity. In SCID mouse fibroblasts deficient in DNA-PK activity, BBI failed to reduce the amount of radiation-induced dicentric chromosomes and the radioprotective effect was absent. Likewise, cells expressing mt.TP53 did not show radioprotection by BBI. CONCLUSIONS: It was observed that BBI exerts its radioprotective effect by a reduction of incorrect DNA repair, resulting in a reduced amount of dicentric chromosomes. This effect on the fidelity of DNA repair is TP53 dependent and correlated with induction of DNA-PK activity.
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