Chromosome aberrations induced by light ions: Monte Carlo simulations based on a mechanistic model

Purpose: To investigate the mechanisms underlying the induction of chromoso me aberrations by ionizing radiation, focusing attention on DNA damage seve rity, interphase chromosome geometry and the distribution of DNA strand bre aks. Methods: An ab initio biophysical model of aberration induction in human ly mphocytes specific for light ions was developed, based on the assumption th at 'complex lesions' (clustered DNA breaks) produce aberrations, whereas le ss severe breaks are repaired. It was assumed that interphase chromosomes a re spatially localized and that chromosome break free-ends rejoin pairwise randomly; the unrejoining of a certain fraction of free-ends was assumed to be possible, and small fragments were neglected in order to reproduce expe rimental conditions. The yield of different aberrations was calculated and compared with some data obtained using Giemsa or FISH techniques. Results: Dose-response curves for dicentrics and centric rings (Giemsa) and for reciprocal, complex and incomplete exchanges (FISH) were simulated; th e ratio between complex and reciprocal exchanges was also calculated as a f unction of particle type and LET. The results showed agreement with data fr om lymphocyte irradiation with light ions. Conclusions: The results suggest that clustered DNA breaks are a critical d amage type for aberration induction and that interphase chromosome localiza tion plays an important role. Moreover, the effect of a given particle type is related both to the number of induced complex lesions and to their spat ial distribution.