From radiation-induced chromosome damage to cell death: modelling basic mechanisms and applications to boron neutron capture therapy.

Cell death is a crucial endpoint in radiation-induced biological damage: on one side cell death is a reference endpoint to characterize the action of radiation in biological targets, on the other side any cancer therapy aims to kill tumour cells. Starting from Lea’s target theory, many models have been proposed to interpret radiation-induced cell killing; after briefly discussing some of these models, in this paper we will present a mechanistic approach based on an experimentally observed link between chromosome aberrations and cell death. More specifically, a model and a Monte Carlo code originally developed for chromosome aberrations were extended to simulate radiation-induced cell death applying an experimentally observed one-to-one relationship between the average number of “lethal aberrations” (dicentrics, rings and deletions) per cell and –lnS, being S the fraction of surviving cells. Although such observation was related to X rays, in the present work the approach was applied also to protons and alpha particles. The good agreement between simulation outcomes and literature data provided a model validation for different radiation types. The same approach was then successfully applied to simulate the survival of cells enriched with Boron and irradiated with thermal neutrons at the Triga Mark II reactor in Pavia, to mimic a typical treatment for Boron Neutron Capture Therapy.