Abstract

A biophysical model and Monte Carlo code simulating cell death and chromosome damage by different ionizing radiations, including those used in hadrontherapy, will be presented. The model, called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations [1] , [2] ), assumes that DNA “Cluster Lesions” (CLs) can produce chromosome aberrations (i.e., distance-dependent incorrect rearrangements of chromosome fragments), some of which can lead to cell death. The mean number of CLs per Gy and per cell is the first adjustable parameter; the second parameter is either the probability that a chromosome fragment remains unrejoined, or the characteristic distance governing chromosome-fragment rejoining, depending on which model version is used. Comparisons with experimental dose-response curves for cell survival and/or chromosome aberrations allowed tuning the model parameters for a radioresistant cell line (representative of tumour cell response) and a normal one (representative of the response of healthy tissues), thus producing a database of CL yields for different particle types and LET values. Since the CL yield for a given particle type showed a linear-quadratic increase with LET, a fit of such database allows performing full predictions of cell death and chromosome aberrations in principle for any LET value within the range covered by the experiments. Recently, the model was applied to calculate the dependence of cell death and chromosome damage on depth in tissue for SOBP profiles used in different centres, including the CATANA facility for eye melanoma treatment at INFN-LNS and the CNAO hadrontherapy centre in Pavia. In particular for protons, the biological effectiveness was found to increase in the distal region, and significant levels of damage beyond the distal dose fall-off were observed. In line with other studies, these results suggest that assuming a constant biological effectiveness along a proton SOBP may be sub-optimal.

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