Monte Carlo Simulation of Double-Strand Break Induction and Conversion after Ultrasoft X-rays Irradiation

Abstract

This paper estimates the yields of DNA double-strand breaks (DSBs) induced by ultrasoft X-rays and uses the DSB yields and the repair outcomes to evaluate the relative biological effectiveness (RBE) of ultrasoft X-rays. We simulated the yields of DSB induction and predicted them in the presence and absence of oxygen, using a Monte Carlo damage simulation (MCDS) software, to calculate the RBE. Monte Carlo excision repair (MCER) simulations were also performed to calculate the repair outcomes (correct repairs, mutations, and DSB conversions). Compared to 60Co γ-rays, the RBE values for ultrasoft X-rays (titanium K-shell, aluminum K-shell, copper L-shell, and carbon K-shell) for DSB induction were respectively 1.3, 1.9, 2.3, and 2.6 under aerobic conditions and 1.3, 2.1, 2.5, and 2.9 under a hypoxic condition (2% O2). The RBE values for enzymatic DSBs were 1.6, 2.1, 2.3, and 2.4, respectively, indicating that the enzymatic DSB yields are comparable to the yields of DSB induction. The synergistic effects of DSB induction and enzymatic DSB formation further facilitate cell killing and the advantage in cancer treatment.

A double‐strand‐break model for the relative biological effectiveness of electrons based on ionization clustering

“…For example, low‐energetic electrons of a few hundred eV were found to be two to four times more effective in DSB induction in comparison to high‐energetic electrons of 10 5 –10 6 eV as reported in several experimental studies 1–6 (typically performed with low‐energetic photons). This observation is in line with predictions reported in theoretical studies 7–14 …”

“…These data were not directly used to [1][2][3][4][5][6] and simulations. [7][8][9][10][11][12][13][14]60,61 Note that these were determined with various different reference radiation species as indicated by color. Co 𝛾 refers to the photons emitted during the decay of 60 Co.…”

“…The mathematical optimization of the parameters κ and t was performed by simultaneously fitting the results of both quantities listed above to literature data. Corresponding measurement 1–6,56–59 and simulation 7–14,25,26,28,30,38,43,60–63 data were collected from 28 publications. Details on the data are provided in Table in the Supporting Information.…”

“…12 The fast Monte Carlo damage simulation (MCDS) of Semenenko et al from 2004 30 provides estimates of DSB yields and other DNA damages after irradiation of a cell by monoenergetic electrons and other radiation species. 7,31 In the algorithm, first, the expected number of elementary damages produced in a cell by a specified radiation dose is distributed randomly in a DNA segment. Second, the distribution of elementary damages is subdivided into the final lesions.…”

The Effect of Hypoxia on Relative Biological Effectiveness and Oxygen Enhancement Ratio for Cells Irradiated with Grenz Rays

“…The MCDS-derived RBE values for DSB induction are reported in several studies [ 30 , 78 , 79 ], including a comparison with experimental data for soft X-rays and protons [ 30 , 80 , 81 , 82 , 83 ]. The results for track structure simulations for cells irradiated with lower energy photon beams, such as 4.55 kV X-rays ( LET = 6.57 keV/μm), show that the DNA damage profiles obtained by MCDS are up to 7% different to those derived by these track structure simulations ( Table 2 ).…”