The role of shock waves on the biodamage induced by ion beam radiation

Vera, Pablo de; Surdutovich, Eugene; Solov’yov, Andrey V.

doi:10.1186/s12645-019-0050-3

Cited by 16 publications

(9 citation statements)

References 95 publications

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“…Moreover, the RBE data have been acquired for only a handful of cell lines, tissues, and endpoints. The energy of proton beam at the middle and end of Bragg peak and its energy distribution, mainly depends on the target depth, considerably affects the track structure of the protons that is crucial for DNA damage [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Singh

Eley

Mahmood

et al. 2021

Cancers

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Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.

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Section: Introductionmentioning

confidence: 99%

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Singh

Eley

Mahmood

et al. 2021

Cancers

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“…[ 21,26,35 ] The discontinuity in pressure in a nanometric cylinder around the ion's path results in the formation of a cylindrical shock wave propagating away from the path. [ 21,33,59 ]…”

Section: Methodsmentioning

confidence: 99%

“…The shock wave is induced by the ion travelling through the aqueous environment, where it loses its energy by electronic excitations and ionizations. A large amount of the ion's energy is deposited in a radius of 1 nm around the ion's track, generating the shock wave [19,50,51]. To emulate this process, the shock wave is introduced to the final equilibrated structure of the system obtained from step 5 in the workflow (see Fig.…”

Section: E Reactive Charmm Force Field Equilibration (Step 5)mentioning

confidence: 99%

“…Although the direct experimental detection of ion‐induced shock waves is still pending, there is a number of indirect signatures of this phenomenon taking place in biological media. [ 33–35 ] One of the most promising arguments in favor of the shock wave effect is that inclusion of this effect in the multiscale scenario of biodamage with ions [ 26 ] has enabled to reproduce experimentally measured cell survival probabilities and some other radiobiological quantities. [ 34,36 ]…”

Section: Introductionmentioning

confidence: 99%

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Modeling the effect of ion‐induced shock waves and DNA breakage with the reactive CHARMM force field

et al. 2020

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Ion‐induced DNA damage is an important effect underlying ion beam cancer therapy. This article introduces the methodology of modeling DNA damage induced by a shock wave caused by a projectile ion. Specifically it is demonstrated how single‐ and double strand breaks in a DNA molecule could be described by the reactive CHARMM (rCHARMM) force field implemented in the program MBN Explorer. The entire workflow of performing the shock wave simulations, including obtaining the crucial simulation parameters, is described in seven steps. Two exemplary analyses are provided for a case study simulation serving to: (a) quantify the shock wave propagation and (b) describe the dynamics of formation of DNA breaks. The article concludes by discussing the computational cost of the simulations and revealing the possible maximal computational time for different simulation set‐ups.

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“…For that reason, one may expect such large molecular velocities to form nanoscopic shock-waves [20][21][22][23] in the trackstructure as discussed in a series of publications (see for example Refs. [24,25]).…”

Section: Langevin Dynamicsmentioning

confidence: 99%

The effect of non-ionizing excitations on the diffusion of ion species and inter-track correlations in FLASH ultra-high dose rate radiotherapy

Abolfath,

Baikalov,

Bartzsch

et al. 2022

Preprint

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Purpose: We present a microscopic mechanism that accounts for the outward burst of "cold" ion species (IS) in a high-energy particle track due to coupling with "hot" non-ion species (NIS). IS refers to radiolysis products of ionized molecules, whereas NIS refers to non-ionized excitations of molecules in a medium. The interaction is mediated by a quantized field of acoustic phonons, a channel that allows conversion of thermal energy of NIS to kinetic energy of IS, a flow of heat from the outer to the inner core of the track structure.Methods: We perform step-by-step Monte Carlo (MC) simulations of ionizing radiation track structures in water to score the spatial coordinates and energy depositions that form IS and NIS at atto-second time scales. We subsequently calculate the resulting temperature profiles of the tracks with MC track structure simulations and verify the results analytically using the Rutherford scattering formulation. These temperature profiles are then used as boundary conditions in a series of multi-scale atomistic molecular dynamic (MD) simulations that describe the sudden expansion and enhanced diffusive broadening of tracks initiated by the non-equilibrium spectrum of high-energy IS. We derive a stochastic coarse-grained Langevin equation of motion for IS from first-principle MD to describe the irreversible femto-second flow of thermal energy pumping from NIS to IS, mediated by quantized fields of acoustic phonons. A pair-wise Lennard-Jones potential implemented in a classical MD is then employed to validate the results calculated from the Langevin equation.Results: We demonstrate the coexistence of "hot" NIS with "cold" IS in the radiation track structures right after their generation. NIS, concentrated within nano-scales volumes wrapping around IS, are the main source of intensive heat-waves and the outward burst of IS due to femtosecond time scale IS-NIS coupling. By comparing the transport of IS coupled to NIS with identical configurations of non-interacting IS in thermal equilibrium at room temperature, we demonstrate that the energy gain of IS due to the surrounding hot nanoscopic volumes of NIS significantly increases their effective diffusion constants. Comparing the average track separation and the time scale calculated for a deposited dose of 10 Gy and a dose rate of 40 Gy/s, typical values used in FLASH ultra high dose rate (UHDR) experiments, we find that the sudden expansion of tracks and ballistic transport proposed in this work strengthens the hypothesis of inter-track correlations recently introduced to interpret mitigation of the biological responses at the FLASH-UHDR [10].Conclusions: The much higher diffusion constants predicted in the present model suggest higher inter-track chemical reaction rates at FLASH-UHDR, as well as lower intra-track reaction rates. This study explains why research groups relying on the current Monte Carlo frameworks have reported negligible inter-track overlaps, simply because of underestimation of the diffusion constants. We recommend incorporatio...

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The role of shock waves on the biodamage induced by ion beam radiation

Cited by 16 publications

References 95 publications

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Modeling the effect of ion‐induced shock waves and DNA breakage with the reactive CHARMM force field

The effect of non-ionizing excitations on the diffusion of ion species and inter-track correlations in FLASH ultra-high dose rate radiotherapy

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