TY  - JOUR
AU  - Shin, Wook-Geun
AU  - Sakata, Dousatsu
AU  - Lampe, Nathanael
AU  - Belov, Oleg
AU  - Tran, Ngoc Hoang
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
AU  - Đorđević, Miloš
AU  - Bernal, Mario A.
AU  - Bordage, Marie-Claude
AU  - Francis, Ziad
AU  - Kyriakou, Ioanna
AU  - Perrot, Yann
AU  - Sasaki, Takashi
AU  - Villagrasa, Carmen
AU  - Guatelli, Susanna
AU  - Breton, Vincent
AU  - Emfietzoglou, Dimitris
AU  - Incerti, Sebastien
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9961
AB  - 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.
T2  - Cancers
T2  - Cancers
T1  - A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast
VL  - 13
IS  - 19
SP  - 4940
DO  - 10.3390/cancers13194940
ER  - 

@article{
author = "Shin, Wook-Geun and Sakata, Dousatsu and Lampe, Nathanael and Belov, Oleg and Tran, Ngoc Hoang and Petrović, Ivan M. and Ristić-Fira, Aleksandra and Đorđević, Miloš and Bernal, Mario A. and Bordage, Marie-Claude and Francis, Ziad and Kyriakou, Ioanna and Perrot, Yann and Sasaki, Takashi and Villagrasa, Carmen and Guatelli, Susanna and Breton, Vincent and Emfietzoglou, Dimitris and Incerti, Sebastien",
year = "2021",
abstract = "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.",
journal = "Cancers, Cancers",
title = "A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast",
volume = "13",
number = "19",
pages = "4940",
doi = "10.3390/cancers13194940"
}

Shin, W., Sakata, D., Lampe, N., Belov, O., Tran, N. H., Petrović, I. M., Ristić-Fira, A., Đorđević, M., Bernal, M. A., Bordage, M., Francis, Z., Kyriakou, I., Perrot, Y., Sasaki, T., Villagrasa, C., Guatelli, S., Breton, V., Emfietzoglou, D.,& Incerti, S.. (2021). A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast. in Cancers, 13(19), 4940.
https://doi.org/10.3390/cancers13194940

Shin W, Sakata D, Lampe N, Belov O, Tran NH, Petrović IM, Ristić-Fira A, Đorđević M, Bernal MA, Bordage M, Francis Z, Kyriakou I, Perrot Y, Sasaki T, Villagrasa C, Guatelli S, Breton V, Emfietzoglou D, Incerti S. A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast. in Cancers. 2021;13(19):4940.
doi:10.3390/cancers13194940 .

Shin, Wook-Geun, Sakata, Dousatsu, Lampe, Nathanael, Belov, Oleg, Tran, Ngoc Hoang, Petrović, Ivan M., Ristić-Fira, Aleksandra, Đorđević, Miloš, Bernal, Mario A., Bordage, Marie-Claude, Francis, Ziad, Kyriakou, Ioanna, Perrot, Yann, Sasaki, Takashi, Villagrasa, Carmen, Guatelli, Susanna, Breton, Vincent, Emfietzoglou, Dimitris, Incerti, Sebastien, "A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast" in Cancers, 13, no. 19 (2021):4940,
https://doi.org/10.3390/cancers13194940 . .

TY  - JOUR
AU  - Keta, Otilija D.
AU  - Petković, Vladana
AU  - Cirrone, Pablo
AU  - Petringa, Giada
AU  - Cuttone, Giacomo
AU  - Sakata, Dousatsu
AU  - Shin, Wook-Geun
AU  - Incerti, Sebastien
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9875
AB  - Purpose The complex relationship between linear energy transfer (LET) and cellular response to radiation is not yet fully elucidated. To better characterize DNA damage after irradiations with therapeutic protons, we monitored formation and disappearance of DNA double-strand breaks (DNA DSB) as a function of LET and time. Comparisons with conventional γ-rays and high LET carbon ions were also performed.Materials and Methods In the present work, we performed immunofluorescence-based assay to determine the amount of DNA DSB induced by different LET values along the 62 MeV therapeutic proton Spread out Bragg peak (SOBP) in three cancer cell lines, i.e. HTB140 melanoma, MCF-7 breast adenocarcinoma and HTB177 non-small lung cancer cells. Time dependence of foci formation was followed as well. To determine irradiation positions, corresponding to the desired LET values, numerical simulations were carried out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions.Results With 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.Conclusions In 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.
T2  - International Journal of Radiation Biology
T1  - DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time
VL  - 97
IS  - 9
SP  - 1229
EP  - 1240
DO  - 10.1080/09553002.2021.1948140
ER  - 

@article{
author = "Keta, Otilija D. and Petković, Vladana and Cirrone, Pablo and Petringa, Giada and Cuttone, Giacomo and Sakata, Dousatsu and Shin, Wook-Geun and Incerti, Sebastien and Petrović, Ivan M. and Ristić-Fira, Aleksandra",
year = "2021",
abstract = "Purpose The complex relationship between linear energy transfer (LET) and cellular response to radiation is not yet fully elucidated. To better characterize DNA damage after irradiations with therapeutic protons, we monitored formation and disappearance of DNA double-strand breaks (DNA DSB) as a function of LET and time. Comparisons with conventional γ-rays and high LET carbon ions were also performed.Materials and Methods In the present work, we performed immunofluorescence-based assay to determine the amount of DNA DSB induced by different LET values along the 62 MeV therapeutic proton Spread out Bragg peak (SOBP) in three cancer cell lines, i.e. HTB140 melanoma, MCF-7 breast adenocarcinoma and HTB177 non-small lung cancer cells. Time dependence of foci formation was followed as well. To determine irradiation positions, corresponding to the desired LET values, numerical simulations were carried out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions.Results With 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.Conclusions In 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.",
journal = "International Journal of Radiation Biology",
title = "DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time",
volume = "97",
number = "9",
pages = "1229-1240",
doi = "10.1080/09553002.2021.1948140"
}

Keta, O. D., Petković, V., Cirrone, P., Petringa, G., Cuttone, G., Sakata, D., Shin, W., Incerti, S., Petrović, I. M.,& Ristić-Fira, A.. (2021). DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time. in International Journal of Radiation Biology, 97(9), 1229-1240.
https://doi.org/10.1080/09553002.2021.1948140

Keta OD, Petković V, Cirrone P, Petringa G, Cuttone G, Sakata D, Shin W, Incerti S, Petrović IM, Ristić-Fira A. DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time. in International Journal of Radiation Biology. 2021;97(9):1229-1240.
doi:10.1080/09553002.2021.1948140 .

Keta, Otilija D., Petković, Vladana, Cirrone, Pablo, Petringa, Giada, Cuttone, Giacomo, Sakata, Dousatsu, Shin, Wook-Geun, Incerti, Sebastien, Petrović, Ivan M., Ristić-Fira, Aleksandra, "DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time" in International Journal of Radiation Biology, 97, no. 9 (2021):1229-1240,
https://doi.org/10.1080/09553002.2021.1948140 . .

TY  - JOUR
AU  - Sakata, Dousatsu
AU  - Belov, Oleg
AU  - Bordage, Marie-Claude
AU  - Emfietzoglou, Dimitris
AU  - Guatelli, Susanna
AU  - Inaniwa, Taku
AU  - Ivanchenko, Vladimir
AU  - Karamitros, Mathieu
AU  - Kyriakou, Ioanna
AU  - Lampe, Nathanael
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
AU  - Shin, Wook-Geun
AU  - Incerti, Sebastien
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9751
AB  - Ionising radiation induced DNA damage and subsequent biological responses to it depend on the radiation's track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic "fully integrated" MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of gamma -H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.
T2  - Scientific Reports
T1  - Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA
VL  - 10
IS  - 1
SP  - 20788
DO  - 10.1038/s41598-020-75982-x
ER  - 

@article{
author = "Sakata, Dousatsu and Belov, Oleg and Bordage, Marie-Claude and Emfietzoglou, Dimitris and Guatelli, Susanna and Inaniwa, Taku and Ivanchenko, Vladimir and Karamitros, Mathieu and Kyriakou, Ioanna and Lampe, Nathanael and Petrović, Ivan M. and Ristić-Fira, Aleksandra and Shin, Wook-Geun and Incerti, Sebastien",
year = "2020",
abstract = "Ionising radiation induced DNA damage and subsequent biological responses to it depend on the radiation's track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic "fully integrated" MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of gamma -H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.",
journal = "Scientific Reports",
title = "Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA",
volume = "10",
number = "1",
pages = "20788",
doi = "10.1038/s41598-020-75982-x"
}

Sakata, D., Belov, O., Bordage, M., Emfietzoglou, D., Guatelli, S., Inaniwa, T., Ivanchenko, V., Karamitros, M., Kyriakou, I., Lampe, N., Petrović, I. M., Ristić-Fira, A., Shin, W.,& Incerti, S.. (2020). Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA. in Scientific Reports, 10(1), 20788.
https://doi.org/10.1038/s41598-020-75982-x

Sakata D, Belov O, Bordage M, Emfietzoglou D, Guatelli S, Inaniwa T, Ivanchenko V, Karamitros M, Kyriakou I, Lampe N, Petrović IM, Ristić-Fira A, Shin W, Incerti S. Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA. in Scientific Reports. 2020;10(1):20788.
doi:10.1038/s41598-020-75982-x .

Sakata, Dousatsu, Belov, Oleg, Bordage, Marie-Claude, Emfietzoglou, Dimitris, Guatelli, Susanna, Inaniwa, Taku, Ivanchenko, Vladimir, Karamitros, Mathieu, Kyriakou, Ioanna, Lampe, Nathanael, Petrović, Ivan M., Ristić-Fira, Aleksandra, Shin, Wook-Geun, Incerti, Sebastien, "Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA" in Scientific Reports, 10, no. 1 (2020):20788,
https://doi.org/10.1038/s41598-020-75982-x . .

TY  - JOUR
AU  - Sakata, Dousatsu
AU  - Lampe, Nathanael
AU  - Karamitros, Mathieu
AU  - Kyriakou, Ioanna
AU  - Belov, Oleg
AU  - Bernal, Mario A
AU  - Bolst, David
AU  - Bordage, Marie-Claude
AU  - Breton, Vincent
AU  - Brown, Jeremy M.C.
AU  - Francis, Ziad
AU  - Ivanchenko, Vladimir
AU  - Meylan, Sylvain
AU  - Murakami, Koichi
AU  - Okada, Shogo
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
AU  - Santin, Giovanni
AU  - Sarramia, David
AU  - Sasaki, Takashi
AU  - Shin, Wook-Geun
AU  - Tang, Nicolas
AU  - Tran, Hoang N
AU  - Villagrasa, Carmen
AU  - Emfietzoglou, Dimitris
AU  - Nieminen, Petteri
AU  - Guatelli, Susanna
AU  - Incerti, Sebastien
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S1120179719300882
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8206
AB  - The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage – radiobiology, radiation physics, radiation protection and, in particular, medical physics – requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC)simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs)and double strand breaks (DSBs)in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%. © 2019 Associazione Italiana di Fisica Medica
T2  - Physica Medica
T1  - Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA
VL  - 62
SP  - 152
EP  - 157
DO  - 10.1016/j.ejmp.2019.04.010
ER  - 

@article{
author = "Sakata, Dousatsu and Lampe, Nathanael and Karamitros, Mathieu and Kyriakou, Ioanna and Belov, Oleg and Bernal, Mario A and Bolst, David and Bordage, Marie-Claude and Breton, Vincent and Brown, Jeremy M.C. and Francis, Ziad and Ivanchenko, Vladimir and Meylan, Sylvain and Murakami, Koichi and Okada, Shogo and Petrović, Ivan M. and Ristić-Fira, Aleksandra and Santin, Giovanni and Sarramia, David and Sasaki, Takashi and Shin, Wook-Geun and Tang, Nicolas and Tran, Hoang N and Villagrasa, Carmen and Emfietzoglou, Dimitris and Nieminen, Petteri and Guatelli, Susanna and Incerti, Sebastien",
year = "2019",
abstract = "The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage – radiobiology, radiation physics, radiation protection and, in particular, medical physics – requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC)simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs)and double strand breaks (DSBs)in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%. © 2019 Associazione Italiana di Fisica Medica",
journal = "Physica Medica",
title = "Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA",
volume = "62",
pages = "152-157",
doi = "10.1016/j.ejmp.2019.04.010"
}

Sakata, D., Lampe, N., Karamitros, M., Kyriakou, I., Belov, O., Bernal, M. A., Bolst, D., Bordage, M., Breton, V., Brown, J. M.C., Francis, Z., Ivanchenko, V., Meylan, S., Murakami, K., Okada, S., Petrović, I. M., Ristić-Fira, A., Santin, G., Sarramia, D., Sasaki, T., Shin, W., Tang, N., Tran, H. N., Villagrasa, C., Emfietzoglou, D., Nieminen, P., Guatelli, S.,& Incerti, S.. (2019). Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA. in Physica Medica, 62, 152-157.
https://doi.org/10.1016/j.ejmp.2019.04.010

Sakata D, Lampe N, Karamitros M, Kyriakou I, Belov O, Bernal MA, Bolst D, Bordage M, Breton V, Brown JM, Francis Z, Ivanchenko V, Meylan S, Murakami K, Okada S, Petrović IM, Ristić-Fira A, Santin G, Sarramia D, Sasaki T, Shin W, Tang N, Tran HN, Villagrasa C, Emfietzoglou D, Nieminen P, Guatelli S, Incerti S. Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA. in Physica Medica. 2019;62:152-157.
doi:10.1016/j.ejmp.2019.04.010 .

Sakata, Dousatsu, Lampe, Nathanael, Karamitros, Mathieu, Kyriakou, Ioanna, Belov, Oleg, Bernal, Mario A, Bolst, David, Bordage, Marie-Claude, Breton, Vincent, Brown, Jeremy M.C., Francis, Ziad, Ivanchenko, Vladimir, Meylan, Sylvain, Murakami, Koichi, Okada, Shogo, Petrović, Ivan M., Ristić-Fira, Aleksandra, Santin, Giovanni, Sarramia, David, Sasaki, Takashi, Shin, Wook-Geun, Tang, Nicolas, Tran, Hoang N, Villagrasa, Carmen, Emfietzoglou, Dimitris, Nieminen, Petteri, Guatelli, Susanna, Incerti, Sebastien, "Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA" in Physica Medica, 62 (2019):152-157,
https://doi.org/10.1016/j.ejmp.2019.04.010 . .