Selective radioprotection of normal tissues by Bowman-birk proteinase inhibitor (BBI) in mice.
OBJECTIVE
The efficacy of radiotherapy is limited by the response of normal tissues within the radiation field. The application of normal-tissue-specific radioprotectors may improve the therapeutic benefit of radiotherapy. The purpose of the present study was to explore the in vivo normal-tissue radioprotective potential of Bowman-Birk proteinase inhibitor (BBI), which acts as a normal-cell-specific radioprotector in vitro.


METHODS
The leg contracture assay in mice, a model system assessing radiation-induced fibrotic processes, was used. To determine whether BBI acts also as a radioprotector of tumors (i. e., FSA and FSAII), the tumor growth delay assay was used.


RESULTS
Radiation induced leg contracture in mice with a maximum of about 8 mm at day 150 after irradiation. Treatment of mice with 100 mg/kg BBI before irradiation reduced leg contracture by > 4 mm, by about 50% (p < 0.05, t-test). Doses < 100 mg/kg were ineffective, and doses > 100 mg/kg did not further increase the degree of radioprotection. By contrast, BBI did not induce radioprotection of either TP53-mutated FSA or TP53-normal FSAII tumor xenografts in mice, which argues for normal-tissue-specific effect.


CONCLUSIONS
BBI acts as a potent selective normal-tissue radioprotector in vitro and in vivo, apparently without protecting tumors, and thus has the potential to improve clinical radiotherapy.
Dittmann
Klaus
K
Division of Radiobiology and Environmental Research, Department of Radiation Oncology, University of Tuebingen, Germany. klaus.dittmann@uni-tuebingen.de
Toulany
Mahmoud
M
Classen
Johannes
J
Heinrich
Vanessa
V
Milas
Luka
L
Rodemann
H Peter
HP
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D005260:Female; D006614:Hindlimb / Q000528:radiation effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology / Q000528:radiation effects; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D011835:Radiation Protection / Q000379:methods*; D011878:Radiotherapy / Q000009:adverse effects / Q000592:standards; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000627:therapeutic use*
D014358:Trypsin Inhibitor, Bowman-Birk Soybean