We evaluate the track segment yield G′ of typical water radiolysis products (eaq−, ·OH and H2O2) under heavy ions (He, C and Fe ions) using a Monte Carlo simulation code in the Geant4-DNA. Furthermore, we reproduce experimental results of ·OH of He and C ions around the Bragg peak energies (< 6 MeV/u). In the relatively high energy region (e.g., > 10 MeV/u), the simulation results using Geant4-DNA have agreed with experimental results. However, the G-values of water radiolysis species have not been properly evaluated around the Bragg peak energies, at which high ionizing density can be expected. Around the Bragg peak energy, dense continuous secondary products are generated, so that it is necessary to simulate the radical–radical reaction more accurately. To do so, we added the role of secondary products formed by irradiation. Consequently, our simulation results are in good agreement with experimental results and previous simulations not only in the high-energy region but also around the Bragg peak. Several future issues are also discussed regarding the roles of fragmentation and multi-ionization to realize more realistic simulations.

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We have been studying the effectiveness of direct action, which induces clustered DNA damage leading to cell killing, relative to indirect action. Here a new criterion Direct Ation-Based Biological Effectiveness (DABBLE) is proposed to understand the contribution of direct action for cell killing induced by C ions. DABBLE is defined as the ratio of direct action to indirect action. To derive this ratio, we describe survival curves of mammalian cells as a function of the number of OH radicals produced 1 ps and 100 ns after irradiation, instead of the absorbed dose. By comparing values on the vertical axis of the survival curves at a certain number of OH radicals produced, we successfully discriminate the contribution of direct action induced by C ions from that of indirect action. DABBLE increases monotonically with increasing linear energy transfer (LET) up to 140 keV/μm and then drops, when the survival curves are described by the number of OH radicals 1 ps after irradiation. The trend of DABBLE is in agreement with that of relative biological effectiveness (RBE) of indirect action. In comparison, the value of DABBLE increases monotonically with LET, when the survival curves are described by the number of OH radicals 100 ns after irradiation. This finding implies that the effectiveness of C ion therapy for cancer depends on the contribution of direct action and we can follow the contribution of direct action over time in the chemical phase.

Monte Carlo track structure simulation is a powerful method for estimating damage induced by water radiolysis products for cell killing. To investigate the influence of multiple ionization for the formation of water radiolysis products under 1 H + , 4 He 2+ , and 12 C 6+ ion beams, a Monte Carlo simulation based on Geant4-DNA was carried out. The G-value of H 2 O 2 increased monotonically with increasing linear energy transfer up to 200 eV/nm. Above 200 eV/nm, the G-value of H 2 O 2 began dropping, but only when the influence of multiple ionization was considered. This trend is in good agreement with the experimental results. Furthermore, we successfully reproduce the experimental results of G-values of HO 2• + O 2•−. The role of the multiple ionization in the production of H 2 O 2 , HO 2 • , O 2 •−, and O 2 is also discussed.

The aim of this work is to estimate the biological effect of targeted radionuclide therapy using Cu-64, which is a well-known Auger electron emitter. To do so, we evaluate the absorbed dose of emitted particles from Cu-64 using the Geant4-DNA Monte Carlo simulation toolkit. The contribution of beta particles to the absorbed dose is higher than that of Auger electrons. The simulation result agrees with experimental ones evaluated using coumarin-3-carboxylic acid chemical dosimeter. The simulation result is also in good agreement with previous ones obtained using fluorescent nuclear track detector. From the results of present simulation (i.e., absorbed dose estimation) and previous biological experiments using two cell lines (i.e., evaluation of survival curves), we have estimated the relative biological effectiveness (RBE) of Cu-64 emitted particles on CHO wild-type cells and xrs5 cells. The RBE of xrs5 cells exposed to Cu-64 is almost equivalent to that with gamma rays and protons and C ions. This result indicates that the radiosensitivity of xrs5 cells is independent of LET. In comparison to this, the RBE on CHO wild-type cells exposed to Cu-64 is significantly higher than gamma rays and almost equivalent to that irradiated with C ions with a linear energy transfer of 70 keV/μm.