DNA damage assessment of human breast and lung carcinoma cells irradiated with protons and carbon ions

Ristić-Fira, Aleksandra; Keta, Otilija; Petković, Vladana; Cammarata, Francesco Paolo; Petringa, Giada; Cuttone, G.; Incerti, S.

doi:10.1080/16878507.2020.1825035

Cited by 3 publications

(3 citation statements)

References 52 publications

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“…In addition, the sensitivity was significantly improved compared to that for PFGE [51]. Petkovic et al [52], Ristic-Fira et al [53], and Keta et al [2] evaluated DNA damage by measuring γ-H2AX for gamma ray and proton beams. The details of the experimental data presented in this study are given in Table 2, while the biochemical background is provided elsewhere [54,55].…”

Section: Simulation Configuration For Validation Study Using a Simplified Human Fibroblast Cellmentioning

confidence: 99%

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

Shin

Sakata

Lampe³

et al. 2021

Cancers

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Accurately modeling the radiobiological mechanisms responsible for the induction of DNA damage remains a major scientific challenge, particularly for understanding the effects of low doses of ionizing radiation on living beings, such as the induction of carcinogenesis. A computational approach based on the Monte Carlo technique to simulate track structures in a biological medium is currently the most reliable method for calculating the early effects induced by ionizing radiation on DNA, the primary cellular target of such effects. The Geant4-DNA Monte Carlo toolkit can simulate not only the physical, but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of biological targets, such as DNA, to assess direct and indirect early DNA damage. In this study, DNA damage induced in a human fibroblast cell was evaluated using Geant4-DNA as a function of incident particle type (gammas, protons, and alphas) and energy. The resulting double-strand break yields as a function of linear energy transfer closely reproduced recent experimental data. Other quantities, such as fragment length distribution, scavengeable damage fraction, and time evolution of damage within an analytical repair model also supported the plausibility of predicting DNA damage using Geant4-DNA.The complete simulation chain application “molecularDNA”, an example for users of Geant4-DNA, will soon be distributed through Geant4.

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Section: Simulation Configuration For Validation Study Using a Simplified Human Fibroblast Cellmentioning

confidence: 99%

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

Shin

Sakata

Lampe³

et al. 2021

Cancers

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“…The results of this simulation study were compared with both experimental [46][47][48][49][50][51][52][53][54][55] and other simulation data, 28,30,31,33 in terms of calculation of the number of strand breaks (SB) and of direct/indirect damage. To generate a direct DNA damage lesion, the energy deposited during a physical interaction should be closer than 3.5 Å to a DNA base (R dir ).…”

Section: Human Cell Geometrymentioning

confidence: 99%

“…Double-strand break (DSB) yield for incident protons as a function of linear energy transfer (LET) for "human cell" geometry. Both simulation and experimental data are included 30,[46][47][48][49][50][51][52][53][54][55]. of Geant4.…”

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confidence: 99%

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Chatzipapas

Tran

Dordevic³

et al. 2023

Precision Radiation Oncology

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Purpose:The scientific community shows great interest in the study of DNA damage induction, DNA damage repair, and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named "molecularDNA", publicly released in the 11.1 version of Geant4 (December 2022).Methods: It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example includes two different DNA-scale geometries of biological targets, namely "cylinders" and "human cell". This public version is based on a previous prototype and includes new features, such as: the adoption of a new approach for the modeling of the chemical stage, the use of the standard DNA damage format to describe radiation-induced DNA damage, and upgraded computational tools to estimate DNA damage response.Results: Simulation data in terms of single-strand break and double-strand break yields were produced using each of the available geometries. The results were compared with the literature, to validate the example, producing less than 5% difference in all cases.Conclusion: "molecularDNA" is a prototype tool that can be applied in a wide variety of radiobiology studies, providing the scientific community with an open-access base for DNA damage quantification calculations. New DNA and cell geometries for the "molecularDNA" example will be included in future versions of Geant4-DNA.

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DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time

Keta

Petković

Cirrone

et al. 2021

International Journal of Radiation Biology

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In this article out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions. ResultsWith the rise of LET values along the therapeutic proton SOBP, the increase of γ-H2AX foci number is detected in the three cell lines up to the distal end of the SOBP, while there is a decrease on its distal fall-off part. With the prolonged incubation time, the number of foci gradually drops tending to attain the residual level. For the maximum number of DNA DSB, irradiation with protons attain higher level than that of γ-rays. Carbon ions produce more DNA DSB than protons but not substantially. The number of residual foci produced by γ-rays is significantly lower than that of protons and particularly carbon ions. Carbon ions do not produce considerably higher number of foci than protons, as it could be expected due to their physical properties. ConclusionsIn situ visualization of γ-H2AX foci reveal creation of more lesions in the three cell lines by clinically relevant proton SOBP than γ-rays. The lack of significant differences in the number of γ-H2AX foci between the proton and carbon ion-irradiated samples suggests an increased complexity of DNA lesions and slower repair kinetics after carbon ions compared to protons. For all three irradiation types, there is no major difference between the three cell lines shortly after irradiations, while later on, the formation of residual foci starts to express the inherent nature of tested cells, therefore increasing discrepancy between them.

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DNA damage assessment of human breast and lung carcinoma cells irradiated with protons and carbon ions

Cited by 3 publications

References 52 publications

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time

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