Atomistic analysis of DNA strand breaks in tritiated water by using Geant4-DNA simulation with knowledge from quantum chemical calculation

The strand breaks of a double strand B-form DNA in tritiated water were studied by using the Geant4-DNA. Previously, we reported that the reactivity of hydroxyl radicals on abstraction of a deoxyribose hydrogen in the indirect effect can be estimated by introducing the effective atomistic volume of moiety associated with the hydrogen site in the Geant4-DNA [1]. The result was consistent with the measured reactivity and the accessibility of hydroxyl radicals to the deoxyribose’s hydrogens calculated by using the quantum molecular dynamics simulation[2]. In this paper, firstly, we studied the hydrogen abstraction of deoxyribose by hydroxyl radicals in terms of the activation energy by using a semi-empirical quantum chemistry program, MOPAC. The reactivity is expressed by the chemical reaction rate and the accessibility between hydroxyl radicals and hydrogens in deoxyribose. The calculated activation energies were small and below 8 kcal/mol for all hydrogens through 1’ to 5’’. The result indicates that the reactivity is more dependent on the accessibility rather than the chemical reaction rate. Secondly, we studied the variation of fraction of the indirect effect in strand breaks by changing criterion of energy threshold for the direct effect. The fractions in the 2.5 keV electron beam simulation were approximately 30% and 90% for the energy threshold of 10.79 eV[3] and 17.5 eV[4], respectively. Since it is known that the indirect effect is dominant in strand breaks for low energy beta-rays, the 17.5 eV energy threshold is suitable. Thirdly, we started to study the influence of target oxygenation, which generates the other reactive oxygen species such as the superoxide anion and its protonated form other than hydroxyl radicals. The Geant4-DNA simulation was performed for water target with various concentration of dissolved oxygen. We also discuss the influence on strand breaks in this paper.