First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line

Authors:   Maria Dagrosa,Martín Crivello,Marina Perona,Silvia Thorp,Gustavo Santa Cruz,Emiliano Pozzi,Mariana Casal,Lisa Thomasz,Romulo Cabrini,Steven Kahl,Guillermo Juvenal,Mario Pisarev
Journal: International Journal of Radiation Oncology Biology Physics
https://doi.org/10.1016/j.ijrobp.2010.07.020
Abstract: Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ( 10BPA) and for 2,4-bis ($alpha$,$beta$-dihydroxyethyl)-deutero-porphyrin IX ( 10BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm 10B) + neutrons, (2) BOPP (10 ppm 10B) + neutrons, (3) neutrons alone, and (4) gamma rays ( 60Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy (±10%) (thermal neutrons flux = 7.5 10 9 n/cm 2 sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 ± 1.1 and 2.4 ± 0.6; CBE for BOPP: 8.0 ± 2.2 and 2.0 ± 1; CBE for BPA: 19.6 ± 3.7 and 3.5 ± 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma. {textcopyright} 2011 Elsevier Inc Printed in the USA. All rights reserved.