DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation-induced damage.

Abstract

Dose distribution in carbon-ion irradiations is generally envisaged to have therapeutic advantages over protons, primarily due to the carbon ion's comparatively higher relative biological effectiveness in the tumor than in the encompassing healthy tissues. The objective of this work was to simulate the overall physical and chemical reactions of primary carbon ions impinging on liquid water and, as such, to investigate the DNA-damage yields in the form of strand breaks (SBs) and in connection with the expected microdosimetric quantities. Using a B-DNA model and Geant4-DNA, we simulated the primary and secondary interactions in a spherical medium of water. Subsequently, we categorized DNA damages based on their complexity utilizing the concept of μ-randomness. We assumed a threshold of 17.5eV for a direct SB and a probability of 0.13 for an indirect SB triggered by chemical reactions of hydroxyl radicals. Microdosimetric quantities were extracted for three cylindrical volumes representing typical subcellular organisms. For fully ionized carbons of 8-256MeV/u, the yield results appeared to be considerably influenced by the chemical reactions-indicating the important role of secondary electrons in inflicting damage. However, it was mostly the direct-damage spectrum that determined the overall shape of the damage spectrum. At all primary energies, it was more probable to break each DNA strand at one point-the two points being less than 10bp apart-than to break only one strand at two random points. Unlike proton's mean-specific-energy results, which showed more sensitivity to the volume increase of the smallest cylinder than of the larger ones, carbon-ion results showed no such sensitivity. The growth of the yield ratio of the single- and double-strand breaks (DSB) with the particle energy was estimated for protons to be about 2 times that of alphas and 92 times that of carbon ions. Unlike the proton results, which suggested significant correlations between the DSB yields and mean-specific (and lineal) energies, carbon ions exhibited no such correlations.