Proximity effects in chromosome aberration induction: Dependence on radiation quality, cell type and dose.

It is widely accepted that, in chromosome-aberration induction, the (mis-)rejoining probability of two chromosome fragments depends on their initial distance, r. However, several aspects of these "proximity effects" need to be clarified, also considering that they can vary with radiation quality, cell type and dose. A previous work performed by the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model has suggested that, in human lymphocytes and fibroblasts exposed to low-LET radiation, an exponential function of the form exp(-r/r0), which is consistent with free-end (confined) diffusion, describes proximity effects better than a Gaussian function. Herein, the investigation was extended to intermediate- and high-LET. Since the r0 values (0.8 μm for lymphocytes and 0.7 μm for fibroblasts) were taken from the low-LET study, the results were obtained by adjusting only one model parameter, i.e. the yield of "Cluster Lesions" (CLs), where a CL was defined as a critical DNA damage producing two independent chromosome fragments. In lymphocytes, the exponential model allowed reproducing both dose-response curves for different aberrations (dicentrics, centric rings and excess acentrics), and values of F-ratio (dicentrics to centric rings) and G-ratio (interstitial deletions to centric rings). In fibroblasts, a good correspondence was found with the dose-response curves, whereas the G-ratio (and, to a lesser extent, the F-ratio) was underestimated. With increasing LET, F decreased and G increased in both cell types, supporting their role as "fingerprints" of high-LET exposure. A dose-dependence was also found at high LET, where F increased with dose and G decreased, possibly due to inter-track effects. We therefore conclude that, independent of radiation quality, in lymphocytes an exponential function can describe proximity effects at both inter- and intra-chromosomal level; on the contrary, in fibroblasts further studies (experimental and theoretical) are needed to explain the strong bias for intra-arm relative to inter-arm exchanges.