Modelling study of the protective role of OH radical scavengers and DNA higher order structures in induction of single- and double-strand break by gamma-radiation

Purpose: To quantify the protective effects of (non-histonic) OH-radical scavengers and DNA higher-order structures in induction of single- and double-strand breaks by gamma rays. Methods: Spatial distributions of energy depositions by gamma rays in liquid water were modelled with the track structure modules of the biophysical simulation code PARTRAC. Such distributions were superimposed on different DNA structure models (e.g. linear DNA, SV40 'minichromosomes' and compact chromatin), and direct energy depositions in the sugar-phosphate were considered as potential (direct) ssbs. The diffusion and interaction of the main chemical species produced in liquid water radiolysis were explicitly simulated, and reactions of OH radicals with the sugar-phosphate were considered as potential (indirect) ssbs. Two ssb on opposite DNA strands within 10 base pairs were considered as one dsb. Yields of ssb and dsb/Gy/Dalton in different DNA target structures were calculated as a function of the •OH mean life time, whose inverse value was taken as representative of the scavenging capacity (SC) of the DNA environment. Results and Conclusions: This work provided a further validation of the models implemented in the PARTRAC code, thus allowing a better understanding of the mechanisms underlying DNA damage. More specifically, the protection due to •OH scavengers was separately quantified with respect to that due to histones and chromatin folding, which could be 'switched off' in the simulations. As expected, for a given value of the environment SC, linear DNA was found to be more susceptible to strand breakage than SV40 minichromosomes, which in turn showed higher damage yields with respect to cellular DNA, due to the larger accessibility offered to OH radicals. Furthermore, by increasing the SC the break yields decreased in all structures and tended to coincide with direct damage yields. Very good agreement was found with available experimental data. Comparisons with data on 'nucleoid' DNA (i.e. unfolded and histone-depleted DNA) also suggested that the experimental procedures used to obtain such structures may lower the environment SC, due to the loss of cellular scavengers.