Biophysical modelling of proximity effects in chromosome aberration production

Although two chromosome breaks induced in proximity are known to have a higher probability of being (mis-)rejoined, several aspects of these “proximity effects” are still unclear. Herein, proximity effects in human lymphocytes and fibroblasts were investigated by the BIANCA biophysical model, describing the dependence of the rejoining probability on the break initial distance, r, either by an exponential function of the form exp(-r/r0), or by a Gaussian function of the form exp(-r2/22). The characteristic distance (r0 or was an adjustable parameter; the only other parameter was the yield of DNA “Cluster Lesions” (CLs), where a CL is defined as a critical damage producing two independent chromosome fragments. The comparison of the simulation outcomes with published experimental and theoretical works showed that an exponential function may describe proximity effects in both considered cell types, and possibly other cells. Since this exponential behavior has been found to be consistent with confined diffusion of break ends, this also suggests that, at the relatively short times required for chromosome aberration production, (confined) diffusion is preferable to other mechanisms. Furthermore, the results suggested that the ratio of dicentrics to centric rings (“F-ratio”) may be a better high-LET fingerprint in lymphocytes, whereas the ratio of acentric to centric rings (“G-ratio”) may be a better one in fibroblasts.