Cell death following BNCT: a theoretical approach based on Monte Carlo simulations.

In parallel to boron measurements and animal studies, investigations on radiation-induced cell death are also in progress in Pavia, with the aim of better characterizing the effects of a BNCT treatment down to the cellular level. Such studies are being carried out not only experimentally but also theoretically, basing on a mechanistic model and a Monte Carlo code. Such model assumes that: 1) only clustered DNA strand breaks can lead to chromosome aberrations; 2) only chromosome fragments within a certain threshold distance can undergo misrejoining; 3) the so-called "lethal aberrations" (dicentrics, rings and large deletions) lead to cell death. After applying the model to normal cells exposed to monochromatic fields of different radiation types, the irradiation section of the code was purposely extended to mimic the cell exposure to a mixed radiation field produced by the 10B(n,α) 7Li reaction, which gives rise to alpha particles and Li ions of short range and high biological effectiveness, and by the 14N(n,p)14C reaction, which produces 0.58 MeV protons. Very good agreement between model predictions and literature data was found for human and animal cells exposed to X- or gamma-rays, protons and alpha particles, thus allowing to validate the model for cell death induced by monochromatic radiation fields. The model predictions showed good agreement also with experimental data obtained by our group exposing DHD cells to thermal neutrons in the TRIGA Mark II reactor of the University of Pavia; this allowed to validate the model also for a BNCT exposure scenario, providing a useful predictive tool to bridge the gap between irradiation and cell death.