Computational demonstration of multiple DNA damages produced by the radiolytic chemical species in an aqueous DNA solution

Abstract

Multiple DNA damage resulting from the single ionisation of a water molecule is the most fundamental process of the initial step of radiobiological effects. The critical size and the chemical lesion types constituting the damage site have not been fully elucidated. We challenged this long-term issue by developing a dynamic Monte Carlo code for the chemical process. The reaction probabilities and the spatial distribution of lesions were theoretically solved as a function of the spur radius and distance between DNA and the initial ionisation position. The results showed that a hydroxyl radical and a hydrated electron from a single spur can concomitantly react within a 10 base pairs DNA to induce a multiple DNA damage site comprising a DNA single-strand break and reductive nucleobase damage; however, the reaction probability is 0.4% or less. Once this combination arises, it strongly compromises the activity of nucleobase excision repair enzymes. The efficiency is comparable to that of DNA double-strand breaks, which have been thought to be a significant cause of cell death. However, a single-spur reaction could be a source of damaged nucleobase misrepair, leading to point mutations in the genome.