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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 freeends was assumed to be possible, and small fragments were neglected in order to reproduce experimental conditions. The yield of di erent 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 e ect of a given particle type is related both to the number of induced complex lesions and to their spatial distribution. [ABSTRACT FROM AUTHOR]

Abstract. This study simulates the exposure of V79 Chinese hamster fibroblasts to low-energy protons, deuterons and alpha particles in the LET range 10-200 keV/ mu m. The starting assumption is that the induction of clustered lesions in DNA is a fundamental step for cell inactivation. A non-homogeneous cell population was simulated by a computer program, using as input measured morphological parameters reported in the literature. Variations in the number of traversals through each cell of the population and in the length of the traversal, depending on actual nuclear thickness and position of the traversal, the energy spread of the incident beam, and the change of LET along the tracks were included in the simulation. Microdosimetric spectra were computed and compared with spectra obtained neglecting particle slowing-down and stochastic aspects of cell morphology. Simulated cell survival was estimated under the assumption that surviving cells are those with no clustered DNA lesions or no passages. The main features of experimental RBE versus LET and particle type were reproduced by the simulations. The influence of stochastic aspects of target-cell morphology and of the energy of the incident particles on survival were investigated under different assumptions about the correlation between morphological parameters. Results support the hypothesis of a relevant role of clustered DNA damage in cell killing and point out the importance of target-cell morphology and its variability in beam dosimetry and computer simulations of low-energy particle radiation effects. [ABSTRACT FROM AUTHOR]

Purpose : To measure clonogenic death of Chinese hamster V79 cells following exposure to a defined number of 4.3 MeV alpha particles (track-averaged LET 105 keV/ mu m). Materials and methods : Cells were irradiated at the radiobiological facility installed at the TTT-3 Tandem accelerator in Naples by using a 'Biostack' approach, which allows the positions of incident tracks relative to cells to be carefully determined. Subcellular structure was identified by fluorescence microscopy, while tracks were visualized by LR-115 solid state nuclear track detectors. Results : Particle hits in the cytoplasm did not significantly affect cell survival, yet survival probability decreased exponentially as a function of the number of nuclear traversals. Measured probability of surviving to exactly one 4.3 MeV alpha -particle traversal in the cell nucleus was 0.67 0.10. Inactivation cross-section was substantially higher than expected from conventional survival curves. However, folding of the data with Poisson statistics showed that survival level expected if a mean of one alpha -particle goes through a nucleus is higher than the measured value after exactly one particle traversal. Conclusions : V79 cells have about 67% probability to survive a single alpha -particle traversal in the cell nucleus. Single-particle survival curves are consistent with conventional dose-survival relationships, once Poisson distribution of traversals is taken into account. [ABSTRACT FROM AUTHOR]