Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB inductions and conversions induced by therapeutic proton beams

Luo, Weiren; Chen, Fang-Hsin; Huang, Ren-Jing; Chen, Yu‐Pin; Hsiao, Ya-Yun

doi:10.1080/09553002.2020.1688883

Cited by 9 publications

(11 citation statements)

References 68 publications

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“…All four pathways (SP BER, LP BER, NER/SP BER, and NER/LP BER) were simulated. The results show that the NER/LP BER pathway has the lowest probability of correct repair and highest probability for mutation and DSB formation, which is similar to the results for 60 Co γ-rays [ 44 ], protons [ 40 ], and helium ions [ 44 ]. These results are ascribed to the fact that the repair of non-DSB clusters occurs mainly through the BER pathway, but other bulk damage is mended by the NER pathway.…”

Section: Methodssupporting

confidence: 78%

“…The types of DNA damage can be grouped into base damage (BD), single strand breaks (SSBs), and DSB. Various complex SSB or DSB, i.e., SSB + , 2SSB, DSB + and DSB ++ , and total SSB and DSB were defined previously [ 40 ]. Briefly, the types and classifications of DNA damage and their abbreviations are: two or more strand breaks on the same strand (SSB + ), two or more strand breaks on opposite strands that do not constitute DSB (2SSB), DSBs with additional break(s) on a strand within 10 base pairs (DSB + ), and more than one DSB within 10 base pairs (DSB ++ ).…”

Section: Methodsmentioning

confidence: 99%

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

Hsiao

Chen

Chan

et al. 2021

IJMS

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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.

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Section: Methodssupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

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

Hsiao

Chen

Chan

et al. 2021

IJMS

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“…Besides RBE, other important cellular responses such as the oxygen enhancement ratio (OER) can also be slightly affected by radiation within this range of LET (18). LET values in the proton entrance region are approximately 1 keV/mm and cannot result in high RBE or low OER (20). Currently, the RBE of clinical proton beams in the proton SOBP region is estimated to be approximately 1.1 to 1.2 (7,(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

et al. 2021

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Proton therapy is a type of hadron radiotherapy used for treating solid tumors. Unlike heavy charged elements, proton radiation is considered to be low LET (Linear Energy Transfer) radiation, like X-rays. However, the clinical SOBP (Spread Out Bragg Peak) proton radiation is considered to be higher in relative biological effectiveness (RBE) than both X-ray and their own entrance region. The RBE is estimated to be 1.1–1.2, which can be attributed to the higher LET at the SOBP region than at the entrance region. In order to clarify the nature of higher LET near the Bragg peak of proton radiation and its potential cytotoxic effects, we utilized a horizontal irradiation system with CHO cells. Additionally, we examined DNA repair mutants, analyzed cytotoxicity with colony formation, and assessed DNA damage and its repair with γ-H2AX foci assay in a high-resolution microscopic scale analysis along with the Bragg peak. Besides confirming that the most cytotoxic effects occurred at the Bragg peak, extended cytotoxicity was observed a few millimeters after the Bragg peak. γ-H2AX foci numbers reached a maximum at the Bragg peak and reduced dramatically after the Bragg peak. However, in the post-Bragg peak region, particle track-like structures were sporadically observed. This region contains foci that are more difficult to repair. The peak and post-Bragg peak regions contain rare high LET-like radiation tracks and can cause cellular lethality. This may have caused unwanted side effects and complexities of outputs for the proton therapy treatment.

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“…The MCDS is not considered as an event-by-event MC code for track structure simulation [15]. On the other hand, this code uses four parameters including σ Sb , f, N min , and n seg for DNA damage calculation which their values have been previously optimized by Semenenko and Stewart [25].…”

Section: Monte Carlo Damage Simulation (Mcds) and Rbe Calculationmentioning

confidence: 99%

“…The reactive oxygen species (ROS) in aerobic conditions have an increased tendency for interaction with DNA molecules which can increase the induced DSB damages. In return, the presence of hypoxic conditions will decrease the DSB yield by about 40% [14,15].…”

Section: Introductionmentioning

confidence: 99%

Impact of spherical applicator diameter on relative biologic effectiveness of low energy IORT X-rays: A hybrid Monte Carlo study

et al. 2020

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Low-kV IORT (Low kilovoltage intraoperative radiotherapy) using INTRABEAM machine and dedicated spherical applicators is a candidate modality for breast cancer treatment. The current study aims to quantify the RBE (relative biologic effectiveness) variations of emitted X-rays from the surface of different spherical applicators and bare probe through a hybrid Monte Carlo (MC) simulation approach. Materials and methods: A validated MC model of INTRABEAM machine and different applicator diameters, based on GEANT4 Toolkit, was employed for RBE evaluation. To doing so, scored X-ray energy spectra at the surface of each applicator diameter/bare probe were used to calculate the corresponding secondary electron energy spectra at various distances inside the water and breast tissue. Then, MCDS (Monte Carlo damage simulation) code was used to calculate the RBE values according to the calculated electron spectra. Results: Presence of spherical applicators can increase the RBE of emitted X-rays from the bare probe by about 22.3%. In return, changing the applicator diameter has a minimal impact (about 3.2%) on RBE variation of emitted X-rays from each applicator surface. By increasing the distance from applicator surface, the RBE increments too, so that its value enhances by about 10% with moving from 2 to 10 mm distance. Calculated RBE values within the breast tissue were higher than those of water by about 4% maximum value. Conclusion: Ball section of spherical IORT applicators can affect the RBE value of the emitted X-rays from INTRABEAM machine. Increased RBE of breast tissue can reduce the prescribed dose for breast irradiation if INTRABEAM machine has been calibrated inside the water.

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Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB inductions and conversions induced by therapeutic proton beams

Cited by 9 publications

References 68 publications

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

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

High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

Impact of spherical applicator diameter on relative biologic effectiveness of low energy IORT X-rays: A hybrid Monte Carlo study

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