title: Bowman-Birk proteinase inhibitor-mediated radioprotection against UV irradiation is TP53-dependent and associated with stimulation of nucleotide excision repair.
abstract: The Bowman-Birk proteinase inhibitor (BBI) has previously been described as a radioprotective agent against ionising radiation. It was demonstrated that BBI is able to significantly increase the clonogenic cell survival of normal fibroblasts when applied before exposure to ultraviolet B (UVB) radiation. In transformed TP53-mutated cell lines, however, the BBI-mediated radioprotection was absent. At the molecular level, the radioprotective effect of BBI can be correlated with BBI-mediated stabilisation of TP53 protein prior to irradiation. Following UVB irradiation, the BBI-treated cells present an accelerated removal of cyclobutane pyrimidine dimers. Thus, the cell and molecular biological data presented suggest that BBI is able to protect cells with functional TP53 from UVB-induced DNA damage. This protective effect is most likely achieved via the activation of the TP53 signalling cascade resulting in the activation of nucleotide excision repair.
authors.affiliation: Department of Radiotherapy, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dittmann
authors.forename: D
authors.initials: D
authors.lastname: Knaus-Dittmann
authors.forename: C
authors.initials: C
authors.lastname: Mayer
authors.forename: H P
authors.initials: HP
authors.lastname: Rodemann
mesh_terms: D015153:Blotting, Western; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology*; D011740:Pyrimidine Dimers / Q000737:chemistry; D011832:Radiation Injuries / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D011480:Protease Inhibitors; D011740:Pyrimidine Dimers; D016159:Tumor Suppressor Protein p53