Proton and light ion RBE for the induction of direct DNA double strand breaks

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, J; Naqa, Issam El

doi:10.1118/1.4944870

Cited by 22 publications

(25 citation statements)

References 48 publications

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“…Trends in SSB yields due to direct and indirect effects were also comparable, with ~10% higher absolute values, whereas the reported ~5% higher yields for alphas due to indirect effects has not been obtained in our study. Another recent modelling study on ion induced direct DNA damage67 revealed for protons with increasing LET (up to 30 keV/μm) a linear decrease of SSB yields and linear increase of DSB yields; for a constant LET value of 24 keV/μm, the SSB yields increased and the DSB yields decreased for He, Li and C with increasing atomic number. The present results on direct DSB yields show the same trends at about 20% lower yields, whereas the about 20% lower direct SSB yields exhibit no clear trend with atomic number and no linear decrease with increasing LET.…”

Section: Discussionmentioning

confidence: 97%

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Friedland

Schmitt

Kundrát

et al. 2017

Sci Rep

163

206

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Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100–200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments.

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Section: Discussionmentioning

confidence: 97%

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Friedland

Schmitt

Kundrát

et al. 2017

Sci Rep

163

206

View full text Add to dashboard Cite

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“…Monte Carlo simulations of radiation-induced DNA damage are, in effect, the modeled embodiment of what we know-or believe we know-from the analysis of a large number of published studies on the induction of DNA damage by ionizing radiation. Monte Carlo simulations are also useful for the generation and testing of hypothesized mechanisms of action [9][10][11][12][13], for developing quantitative algorithms for the classification of clusters of DNA lesions as DSB and non-DSB clusters [1,[14][15][16][17], and for the analysis of measured fragment-size distributions [15,18,19]. The fundamental radiobiologic and clinical significance of particle relative biological effectiveness (RBE) for the end point of DNA damage is reviewed in relation to the RBE for mutagenesis, chromosome aberrations, and reproductive cell survival.…”

Section: Introductionmentioning

confidence: 99%

Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Stewart

2018

International Journal of Particle Therapy

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The specific types and numbers of clusters of DNA lesions, including both DNA doublestrand breaks (DSBs) and non-DSB clusters, are widely considered 1 of the most important initiating events underlying the relative biological effectiveness (RBE) of the light ions of interest in the treatment of cancer related to megavoltage x-rays and 60 Co crays. This review summarizes the categorization of DNA damage, reviews the underlying mechanisms of action by ionizing radiation, and quantifies the general trends in DSB and non-DSB cluster formation by light ions under normoxic and anoxic conditions, as predicted by Monte Carlo simulations that reflect the accumulated evidence from decades of research on radiation damage to DNA. The significance of the absolute and relative numbers of clusters and the local complexity of DSB and non-DSB clusters are discussed in relation to the formation of chromosome aberrations and the loss of cell reproductive capacity. Clinical implications of the dependence of DSB induction on ionization density is reviewed with an eye towards increasing the therapeutic ratio of proton and carbon ion therapy through the explicit optimization of RBE-weighted dose.

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“…A pre-calculated nanodosimetric database with high precise has been published by Ramos et al 42 It consists of nanodosimetric quantities (M 1 ; M C 2 1 ; F 2 ; F C 2 3 ) defined in a cylinder target volume of 2.3 nm diameter and 3.4 nm length corresponding to a DNA segment of 10 base pairs of monoenergetic fully ionized charged particles (proton, 4 He, 7 Li, 9 Be, 11 B, 12 C, 14 N, 16 O) with energies ranging from 1 MeV/u to 1000 MeV/u. The data were simulated with TOPAS-nBio 43,44 extension of the TOPAS simulation software, 45 layered on the top of Geant4DNA 31,46 (version 10.2.p02).…”

Section: Pre-calculated Nanodosimetric Databasementioning

confidence: 99%

“…However, more and more findings have shown that the initial radiation damage to cells is closely related to the ionization cluster size generated by charged particles on the DNA scale. [12][13][14][15][16] Therefore, a more suitable tool for track structure description may be nanodosimetry. 17 In nanodosimetry, [18][19][20][21][22][23][24][25] the track structure of charged particles is characterized by the frequency distributions of the ionization cluster size (ICS), that is, the number of ionizations produced within a target volume in nanoscale.…”

Section: Introductionmentioning

confidence: 99%

Nanodosimetric quantities and RBE of a clinically relevant carbon‐ion beam

Dai

Liu

et al. 2019

Medical Physics

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Purpose Although carbon‐ion therapy is becoming increasingly attractive to the treatment of tumors, details about the ionization pattern formed by therapeutic carbon‐ion beam in tissue have not been fully investigated. In this work, systematic calculations for the nanodosimetric quantities and relative biological effectiveness (RBE) of a clinically relevant carbon‐ion beam were studied for the first time. Methods The method combining both track structure and condensed history Monte Carlo (MC) simulations was adopted to calculate the nanodosimetric quantities. Fragments and energy spectra at different positions of the radiation field of a clinically relevant carbon‐ion pencil beam were generated by means of MC simulations in water. Nanodosimetric quantities such as mean ionization cluster size (M1), the first moment of conditional cluster size (M1C2), cumulative probability (F2), and conditional cumulative probability (F3C2) at these positions were then acquired based on the spectra and the pre‐calculated nanodosimetric database created by track structure MC simulations. What’s more, a novel approach to calculate RBE based on the said nanodosimetric quantities was introduced. The RBE calculations were then conducted for the carbon‐ion beam at different water‐equivalent depths. Results Lateral distributions at various water‐equivalent depths of both the nanodosimetric quantities and RBE values were obtained. The values of M1, M1C2, F2, and F3C2 were 1.49, 2.67, 0.30, and 0.38 at the plateau at the beam central axis and maximized at 2.79, 5.69, 0.47, and 0.68 at the depths around the Bragg peak, respectively. At a given depth, M1 and F2 decreased laterally with increasing the distance to the beam central axis while M1C2 and F3C2 remained nearly unchanged at first and then decreased except for M1C2 at the rising edge of the Bragg peak. The calculated RBE values were 1.07 at the plateau and 3.13 around the Bragg peak. Good agreement between the calculated RBE values and experimental data was obtained. Conclusions Different nanodosimetric quantities feature the track structure of therapeutic carbon‐ion beam in different manners. Detailed ionization patterns generated by carbon‐ion beam could be characterized by nanodosimetric quantities. Moreover the combined method adopted in this work to calculate nanodosimetric quantities is not only valid but also convenient. Nanodosimetric quantities are significantly helpful for the RBE calculations in carbon‐ion therapy.

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Proton and light ion RBE for the induction of direct DNA double strand breaks

Abstract: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate RBEDSB (direct). In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.

Cited by 22 publications

References 48 publications

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Nanodosimetric quantities and RBE of a clinically relevant carbon‐ion beam

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