Insight into the mechanisms underlying tumor response to boron neutron capture therapy in the hamster cheek pouch oral cancer model.
OBJECTIVE
The therapeutic success of different boron neutron capture therapy (BNCT) protocols employing the hamster cheek pouch oral cancer model has been previously reported by our laboratory. The aim of this study was to explore potential mechanisms of BNCT-induced damage to tumor in terms of potential inhibition in DNA synthesis and induction of apoptosis in the tumors that underwent partial remission following application of the different BNCT protocols in this model.


METHODS
We evaluated DNA synthesis employing incorporation of 5-bromo-2'-deoxyuridine as an end-point. Apoptosis was evaluated by immunohistochemistry employing the deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling technique and Bax and Bcl-2 labeling. These studies were performed in tumors that underwent partial remission 1-30 days post-BNCT mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) or (BPA + GB-10).


RESULTS
BNCT exerted a marked inhibitory effect on DNA synthesis in tumors for all the protocols under study. The inhibitory effect of BPA-BNCT occurred as soon as 1 day post-treatment (P < 0.001). Conversely, the effect of GB-10-BNCT became apparent 7-14 days after therapy (P < 0.001) and was sustained until killed at 30 days post-treatment (P < 0.001). (GB-10 + BPA)-BNCT exerted a rapid and persistent effect, conceivably because of the combined effect of BNCT mediated by both boron compounds. The apoptosis studies did not show differences between the pre-treatment group and any of the BNCT groups.


CONCLUSIONS
One of the mechanisms involved in BNCT-induced tumor control in our model would be an inhibitory effect on DNA synthesis. Apoptosis does not seem to have a significant role in BNCT-induced tumor control in our model.
Aromando
Romina F
RF
Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina. romina_aromando@yahoo.com.ar
Heber
Elisa M
EM
Trivillin
Verónica A
VA
Nigg
David W
DW
Schwint
Amanda E
AE
Itoiz
María E
ME
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001896:Boron Compounds / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002610:Cheek; D006224:Cricetinae; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004195:Disease Models, Animal; D004337:Drug Carriers; D020287:In Situ Nick-End Labeling; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000532:radiotherapy*; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals / Q000627:therapeutic use
D001896:Boron Compounds; D004273:DNA, Neoplasm; D004337:Drug Carriers; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D010649:Phenylalanine