Role of DNA/chromatin organisation and scavenging capacity in USX-and proton-induced DNA damage

DNA higher-order structures and (non-histonic) OH radical scavengers have well known protective effects in the induction of single- and double-strand breaks by ionising radiation. In a previous work, such protective roles have been quantified for gamma radiation (Valota et al., Int. J. Radiat. Biol. 79, 2003). As a starting base for the simulations, we used the PARTRAC Monte Carlo code, developed within a collaboration involving the University of Pavia and the GSF institute. The code can reproduce the track structure of photons, electrons, protons and heavier ions in liquid water, and it can simulate the DNA content of a human cell at different organisation levels, based on an atom-by-atom approach. In this work we extended the calculations to Ultra-Soft X rays (USX) and protons, separately analysing the effects of different radiation types on various DNA structures (i.e. linear DNA, SV40 "minichromosomes" and compact chromatin) as a function of the •OH scavenging capacity (SC). Both for USX and for protons, the calculated damage yields decreased by increasing the SC for the three considered target types. Such decrease can be ascribed to the competition between the reactions OH-DNA and OH-scavenger, which becomes more and more likely by increasing the SC. Furthermore, linear DNA was found to be more radiosensitive than SV40 ‘minichromosomes’, which in turn were more radiosensitive than compact chromatin, which is protected by histones. Comparisons with experimental data by Fulford et al. (Int. J. Radiat. Biol. 77, 2001) relative to USX irradiation showed very good agreement. The dependence of the modulating role played by DNA organisation and scavenging capacity on radiation quality is presented and discussed.