The analysis of the densely populated patterns of radiation-induced foci by a stochastic, Monte Carlo model of DNA double-strand breaks induction by heavy ions.

PURPOSE: To resolve the difficulty in counting merged DNA damage foci in high-LET (linear energy transfer) ion-induced patterns.

MATERIALS AND METHODS: The analysis of patterns of RIF (radiation-induced foci) produced by high-LET Fe and Ti ions were conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei.

RESULTS: The model predicts the spatial and genomic distributions of DNA DSB (double-strand breaks) in a cell nucleus for a particular dose of radiation. We used the model to do analyses for three irradiation scenarios: (i) The ions were oriented perpendicular to the flattened nuclei in a cell culture monolayer; (ii) the ions were parallel to that plane; and (iii) round nucleus. In the parallel scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci.

CONCLUSIONS: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantisation of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiment using proteins that detect DNA damage.