BIANCA, a biophysical model of cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy

An upgraded version of the BIANCA II biophysical model, which describes more realistically interphase chromosome organization and the link between chromosome aberrations and cell death, was applied to V79 and AG01522 cells exposed to protons, C-ions and He-ions over a wide LET interval (0.6-502 keV mu m(-1)), as well as proton-irradiated U87 cells. The model assumes that (i) ionizing radiation induces DNA 'cluster lesions' (CLs), where by definition each CL produces two independent chromosome fragments; (ii) fragment (distance-dependent) mis-rejoining, or un-rejoining, produces chromosome aberrations; (iii) some aberrations lead to cell death. The CL yield, which mainly depends on radiation quality but is also modulated by the target cell, is an adjustable parameter. The fragment un-rejoining probability, f, is the second, and last, parameter. The value of f, which is assumed to depend on the cell type but not on radiation quality, was taken from previous studies, and only the CL yield was adjusted in the present work. Good agreement between simulations and experimental data was obtained, suggesting that BIANCA II is suitable for calculating the biological effectiveness of hadrontherapy beams. For both V79 and AG01522 cells, the mean number of CLs per micrometer was found to increase with LET in a linear-quadratic fashion before the over-killing region, where a less rapid increase, with a tendency to saturation, was observed. Although the over-killing region deserves further investigation, the possibility of fitting the CL yields is an important feature for hadrontherapy, because it allows performing predictions also at LET values where experimental data are not available. Finally, an approach was proposed to predict the ion-response of the cell line(s) of interest from the ion-response of a reference cell line and the photon response of both. A pilot study on proton-irradiated AG01522 and U87 cells, taking V79 cells as a reference, showed encouraging results.