Numerical insight into the Dual Radiation Action Theory

This work studies the first and second order mechanisms for the induction of lethal lesions in DNA after irradiation with protons and α-particles. The purpose is to numerically study the mechanisms behind the Dual Radiation Action Theory (DRAT) for these heavy particles. A genetic material geometrical model with atomic resolution is used. It accounts for the explicit position of 5.47 × 10⁹ base pairs, organized up to the chromatin level. The GEANT4-DNA Monte Carlo code was employed to simulate the interaction of these ions with the genetic material model. The number of lethal lesions induced by one- and two-track mechanisms was determined as a function of dose. Values of the α/β ratio were estimated as well as corresponding relative biological effectiveness (RBE). The number of lethal lesions produced by one-track and two-track mechanisms depends on the dose and squared dose, respectively, as predicted by the DRAT. RBE values consistent with experimental results were found, at least for LET below ∼100 keV/μm. Double strand break spatial distributions are qualitatively analyzed. According to this work, the α parameter determined from cellular surviving curves depends on both the physical α and β parameters introduced here, and on the specific energy deposited by a single track into the region of interest. We found an increment of the β parameter with LET, yet at a slower rate than α so that the α/β ratio increases with LET. In addition, we observed and explained the saturation of the α parameter as the dose increases above ∼6 Gy.