Radioprotection of normal tissue to improve radiotherapy: the effect of the Bowman Birk protease inhibitor.
Specific radioprotection of normal tissue represents a promising approach to improve radiotherapy. The ultimate feature of a normal tissue selective radioprotector is that tumor tissue is excluded from protection. Radioprotectors of the current generation, such as Ethyol, are not explicit normal tissue specific. In contrast, the Bowman Birk protease inhibitor, which is known to prevent in vitro and in vivo radiation-induced carcinogenesis, was found to be normal tissue specific. Moreover, the molecular restrictions for this specificity were identified. The radioprotective effect is dependent upon the presence of a functional wt. TP53. Since a high amount of tumors have lost TP53 function during tumor development, the clinical application of BBI to protect normal tissue from radiation damage would effectively improve the therapeutic outcome of radiation therapy. We succeeded to identify stimulation of DNA-repair mechanisms, such as nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), as molecular mode of action. These results are in good agreement with the observations that BBI concomitantly exhibits anticarcinogenic effect and radioprotective effects. Taken together, BBI is recommended as a radioprotector for normal tissue expressing wild type TP53 during treatment of tumors characterized by a mutant TP53.
Dittmann
K H
KH
Section of Radiobiology and Molecular Environmental Research, Dept. of Radiation Oncology, Eberhard-Karls-University, Röntgenweg 11, 72076 Tübingen, Germany. klaus.dittmann@uni-tuebingen.de
Mayer
C
C
Rodemann
H P
HP
D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000532:radiotherapy; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D011480:Protease Inhibitors; D011837:Radiation-Protective Agents; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D016159:Tumor Suppressor Protein p53