Cell death is a crucial endpoint in radiation-induced biological damage, since any cancer therapy aims to kill tumour cells and cell death is a reference endpoint to characterize the radiation action in biological targets. Starting from Lea’s target theory, many models have been proposed to interpret radiation-induced cell killing. After discussing the main models of cell survival, in this paper we will present a theoretical approach based on the experimentally observed link between chromosome aberrations and cell death [1]. A mechanistic model and a Monte Carlo code originally developed for chromosome aberrations were extended to simulate radiation-induced cell death adopting a 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 the observation by Cornforth and Bedford was related to normal fibroblasts exposed to X rays, in the present work the approach was applied also to intermediate- and high-LET radiation. The good agreement between simulation outcomes and literature data provided a model validation for normal cells exposed to 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 BNCT treatment.

From radiation-induced chromosome damage to cell death: modelling basic mechanisms and applications to Boron Neutron Capture Therapy

BALLARINI, FRANCESCA;BORTOLUSSI, SILVA;CLERICI, ANNA MARIA;FERRARI, CINZIA;PROTTI, NICOLETTA;ALTIERI, SAVERIO
2009-01-01

Abstract

Cell death is a crucial endpoint in radiation-induced biological damage, since any cancer therapy aims to kill tumour cells and cell death is a reference endpoint to characterize the radiation action in biological targets. Starting from Lea’s target theory, many models have been proposed to interpret radiation-induced cell killing. After discussing the main models of cell survival, in this paper we will present a theoretical approach based on the experimentally observed link between chromosome aberrations and cell death [1]. A mechanistic model and a Monte Carlo code originally developed for chromosome aberrations were extended to simulate radiation-induced cell death adopting a 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 the observation by Cornforth and Bedford was related to normal fibroblasts exposed to X rays, in the present work the approach was applied also to intermediate- and high-LET radiation. The good agreement between simulation outcomes and literature data provided a model validation for normal cells exposed to 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 BNCT treatment.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/207768
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