Effect of DNA repair inhibition during the treatment of thyroid carcinoma by BNCT.

RODRIGUEZ C; CARPANO M,; THORP S; POZZI E; CUROTTO P; JUVENAL G; PISAREV M; DAGROSA MA

Mar del Plata, Buenos Aires

Congreso; LXI Reunion Anual de la Sociedad Argentina de Investigacion Clinica; 2016

Sociedad Argentina de Investigacion Clinica

Introduction: Boron Neutron Capture Therapy (BNCT) is based on the nuclear reaction10B (n,) 7Li and it has been proposed as an alternative treatment for tumors that do not respond to conventional therapies. Poorly differentiated thyroid carcinoma does not uptake radioactive iodine and therefore the therapeutic dose of this halogen is useless. Previously we determined that after BNCT, DNA double strand break repair pathway by Homologous Recombination (HR), is activated while Non Homologous End Joining (NHEJ) pathway is not. Rad51, HRmain enzyme, is synthesizedafter the treatment and this increase is consistent with DNA repair after 24 hours of the irradiation. These results indicate that there is a specific response to BNCT and cellular rescue mechanisms are activated causing a decrease in the efficacy of the therapy. In order to reducenon desirable effects of repair, we used the specific Rad51 inhibitor B02 [(E)-3-benzyl-2-(2-(pyridin-3-yl) vinyl) quinazolin-4(3H)-one] during the treatment. It has been demonstrated that this molecule specifically inhibited Rad51 repairing activity and in consequence decreases tumor cell survival after different kind of treatments. The aim of this work was to evaluate the efficacy of BNCT in vitrousing B02 during the treatment.Materials and Methods:cells from a human follicular thyroid carcinoma (WRO) were incubated with or without BPA (0,14 M) and with or without B02 (5 M) and after 16 hours were irradiated with a thermal neutron flux in the RA-3 Nuclear Reactor Facility. After 72 hours cell survival was determined by the MTT method and DNA damage by immunofluorescence of H2AX. Results: when B02 (5 M) was incorporated into the culture medium before the irradiation with a neutron beam only or neutron beam plus BPA, the cell survival decrease significantly respect to the groups without the addition of B02 (BNCT+B02 and NCT+B02 at 5 Gy vs C, p