Modeling of DNA fragmentation induced in human fibroblasts by ⁵⁶Fe ions.

In this work we have compared the pattern of DNA fragmentation (in the size range 1-5700 kbp) induced in human fibroblasts by gamma-rays with that induced by Fe ions with an energy of 115 MeV/u; Fe ions are considered of biological significance for radiation protection issues during long term astronauts' travels. The study has taken into account the comparison of the experimental fragmentation spectra, their analysis performed through the implementation of a phenomenological model, and Monte Carlo simulations performed with the PARTRAC code. The phenomenological method characterizes in an approximate but simple way the nonrandom nature of the experimental fragment distribution caused by high LET radiation; it has the advantage to take into account in a detailed way the background fragmentation. The PARTRAC simulations, on the other hand, thanks to the accurate representation of the chromatin geometry and of the physical and physico-chemical processes associated with the energy deposition by radiation, offer the possibility to compute the spectra and to compare them with the experimental data. We found a satisfactory agreement between the experimental data and the results obtained with PARTRAC, recently upgraded with the implementation of ions heavier than alpha particles; this agreement represents a first validation of the code. A relevant result is represented by the very high number of fragments that, according to the Monte Carlo simulations, are produced by iron ions in the size range <1 kbp: half of the total number of radiation induced fragments is given by fragments in this size range. This is consistent with another important result, i.e., the very high DSB correlation that is found through the GBS model in the lower part of the experimental size range (1-9 kbp) for iron ions. The consequence of this large production of fragments smaller than 1 kbp, undetected experimentally, is the large difference between the experimental and theoretical values of the RBE for DSB production, given respectively by 1.34 and 2.39