PURPOSE: To investigate the mechanisms underlying the induction of chromosome aberrations by ionizing radiation, focusing attention on DNA damage severity, interphase chromosome geometry and the distribution of DNA strand breaks. METHODS: An ab initio biophysical model of aberration induction in human lymphocytes specific for light ions was developed, based on the assumption that 'complex lesions' (clustered DNA breaks) produce aberrations, whereas less severe breaks are repaired. It was assumed that interphase chromosomes are 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 experimental 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; the ratio between complex and reciprocal exchanges was also calculated as a function of particle type and LET. The results showed agreement with data from lymphocyte irradiation with light ions. CONCLUSIONS: The results suggest that clustered DNA breaks are a critical damage type for aberration induction and that interphase chromosome localization 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 spatial distribution.
PURPOSE: To investigate the mechanisms underlying the induction of chromosome aberrations by ionizing radiation, focusing attention on DNA damage severity, interphase chromosome geometry and the distribution of DNA strand breaks. METHODS: An ab initio biophysical model of aberration induction in human lymphocytes specific for light ions was developed, based on the assumption that 'complex lesions' (clustered DNA breaks) produce aberrations, whereas less severe breaks are repaired. It was assumed that interphase chromosomes are 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 experimental 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; the ratio between complex and reciprocal exchanges was also calculated as a function of particle type and LET. The results showed agreement with data from lymphocyte irradiation with light ions. CONCLUSIONS: The results suggest that clustered DNA breaks are a critical damage type for aberration induction and that interphase chromosome localization 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 spatial distribution.
Authors: Werner Hofmann; Wei Bo Li; Werner Friedland; Brian W Miller; Balázs Madas; Manuel Bardiès; Imre Balásházy Journal: Radiat Environ Biophys Date: 2019-12-21 Impact factor: 1.925