Evaluation of the Yield of DNA Double-Strand Breaks for Carbon Ions Using Monte Carlo Simulation and DNA Fragment Distribution.

Purpose: The aim of this work was to provide a method to evaluate the yield of DNA double-strand breaks (DSBs) for carbon ions, overcoming the bias in existing methods due to the nonrandom distribution of DSBs.

Methods And Materials: A previously established biophysical program based on the radiation track structure and a multilevel chromosome model was used to simulate DNA damage induced by x-rays and carbon ions. The fraction of activity retained (FAR) as a function of absorbed dose or particle fluence was obtained by counting the fraction of DNA fragments larger than 6 Mbp. Simulated FAR curves for the 250 kV x-rays and carbon ions at various energies were compared with measurements using constant-field gel electrophoresis. The doses or fluences at the FAR of 0.7 based on linear interpolation were used to estimate the simulation error for the production of DSBs.

Results: The relative difference of doses at the FAR of 0.7 between simulation and experiment was -8.5% for the 250 kV x-rays. The relative differences of fluences at the FAR of 0.7 between simulations and experiments were -17.5%, -42.2%, -18.2%, -3.1%, 10.8%, and -14.5% for the 34, 65, 130, 217, 2232, and 3132 MeV carbon ions, respectively. In comparison, the measurement uncertainty was about 20%. Carbon ions produced remarkably more DSBs and DSB clusters per unit dose than x-rays. The yield of DSBs for carbon ions, ranging from 10 to 16 GbpGy, increased with linear energy transfer (LET) but plateaued in the high-LET end. The yield of DSB clusters first increased and then decreased with LET. This pattern was similar to the relative biological effectiveness for cell survival for heavy ions.

Conclusions: The estimated yields of DSBs for carbon ions increased from 10 GbpGy in the low-LET end to 16 GbpGy in the high-LET end with 20% uncertainty.