Geant4-DNA Monte Carlo Simülasyonları Kullanılarak Klinik BT Maruziyetinin Neden Olduğu DNA Hasarının Moleküler Düzeyde Değerlendirilmesi

Yıl 2026, Cilt: 19 Sayı: 1 , 1 - 14 , 30.03.2026

Veli Çapalı

https://izlik.org/JA74EL56TF

Öz

Bu çalışmada, klinik bilgisayarlı tomografi (BT) maruziyetinden kaynaklanan iyonlaştırıcı radyasyonun biyolojik etkileri Geant4-DNA Monte Carlo simülasyonları kullanılarak moleküler düzeyde araştırılmıştır. DNA hasarı modellemesi, 40 nm kübik voksel içindeki beyin hücresi heterokromatin parçaları için “dnadamage”, “mikrodozimetri” ve “molecularDNA” modelleri kullanılarak gerçekleştirilmiştir. G4EmDNAPhysics fizik modeli kullanılarak DNA ile X-ışını etkileşimleri simüle edilerek tek iplikçik kırılmalarının (SSB'ler), çift iplikçik kırılmalarının (DSB'ler) ve karmaşık kümelenmiş lezyonların kantitatif analizi yapılmıştır. Sonuçlar, klinik BT için tipik olan düşük doz aralığında bile ölçülebilir DNA hasarının meydana geldiğini ve bu hasarın boyutunun doz hesaplama yöntemlerinin doğruluğuna duyarlı olduğunu göstermiştir. Ayrıca çalışma, radyoliz tarafından üretilen reaktif oksijen türlerinin (özellikle hidroksil radikalleri (°OH), süperoksit anyonları (O₂-) ve hidrojen peroksit (H₂O₂)- DNA hasarına aracılık etmedeki kritik rollerini vurgulamıştır. Dimetil sülfoksitin (DMSO) radyasyonun neden olduğu serbest radikalleri temizleme yeteneği, gelecekteki radyoprotektif ajanların geliştirilmesi için değerli bilgiler sağlar. Genel olarak, bu bulgular radyasyon risk değerlendirmesinde moleküler düzeydeki biyolojik etkilerin fiziksel doz ölçütleriyle bütünleştirilmesinin gerekliliğinin altını çizmektedir ve tanısal radyolojik prosedürler sırasında normal dokuların korunmasına yönelik yeni stratejilerin geliştirilmesi için bilgi sağlayabilir.

Anahtar Kelimeler

Geant4-DNA , monte carlo simülasyonu , bilgisayarlı tomografi (BT) , DNA hasarı

Etik Beyan

Bu çalışmanın yayınlanmasıyla ilgili herhangi bir etik sorun bulunmamaktadır.

Molecular-Level Assessment of DNA Damage Induced by Clinical CT Exposure Using Geant4-DNA Monte Carlo Simulations

https://izlik.org/JA74EL56TF

Öz

In this study, the biological effects of ionizing radiation from clinical computed tomography (CT) exposure were investigated at the molecular level. Geant4-DNA Monte Carlo simulations were utilized to facilitate this investigation. A DNA damage modeling study was conducted for brain cell heterochromatin fragments within a 40-nm cubic voxel, employing the "dnadamage," "microdosimetry," and "molecularDNA" models. A quantitative analysis of single-strand breaks (SSBs), double-strand breaks (DSBs), and complex clustered lesions was conducted by simulating X-ray interactions with DNA using the G4EmDNAPhysics physics model. The findings indicated that quantifiable DNA damage transpires even within the low-dose range characteristic of clinical CT, and the magnitude of this damage is contingent on the precision of dose calculation methodologies. Furthermore, the study emphasized the pivotal functions of reactive oxygen species (ROS) produced by radiolysis, specifically hydroxyl radicals (°OH), superoxide anions (O₂⁻), and hydrogen peroxide (H₂O₂), in facilitating DNA damage. The capacity of dimethyl sulfoxide (DMSO) to scavenge radiation-induced free radicals offers significant insights into the development of future radioprotective agents. In summary, the present findings underscore the necessity of integrating molecular-level biological effects with physical dose metrics in radiation risk assessment. This integration may inform the development of novel strategies for the protection of normal tissues during diagnostic radiological procedures.

Anahtar Kelimeler

Geant4-DNA , monte carlo simulation , computed tomography (CT) , DNA damage

Etik Beyan

There are no ethical issues regarding the publication of this study.

Kaynakça

• [1] Brenner, D. J. and Hall, E. J., (2007). Computed Tomography an Increasing Source of Radiation Exposure. New England Journal of Medicine, 357(22), 2277–2284. https://doi.org/10.1056/nejmra072149
• [2] Hall, E. J., and Giaccia, A. J. (2018). Radiobiology for the Radiologist. 8th Edition. Wolters Kluwer, 41, 1129-1130. https://doi.org/10.1007/s13246-018-0684-1
• [3] Ward, J. F., (1995). Radiation-induced DNA damage and its repair. Progress in Nucleic Acid Research and Molecular Biology, 35, 95-125. https://doi.org/ 10.1016/s0079-6603(08)60611-x
• [4] Nikjoo, H., O’Neill, P., Wilson, W.E., Goodhead, D.T., (2001). Computational approach for determining the spectrum of DNA damage induced by ionizing radiation. Radiat Res, 156(5 Pt 2):577-83. https://doi.org/10.1667/0033-7587(2001)156[0577:cafdts]2.0.co;2
• [5] Azzam, E. I., Jay-Gerin, J. P., Pain, D. (2012). Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letters, 327(1-2), 48-60. https://doi.org/10.1016/j.canlet.2011.12.012
• [6] Cadet, J., Bellon, S., Douki, T., Frelon, S., Gasparutto, D., Muller, E., Pouget, J.P., Ravanat, J.L., Romieu, A., Sauvaigo, S. (2004). Radiation-induced DNA damage: formation, measurement, and biochemical features. Mutation Research, J Environ Pathol Toxicol Oncol, 23(1):33-43. https://doi.org/10.1615/jenvpathtoxoncol.v23.i1.30.
• [7] Valente, D., Gentileschi, M., Valenti, A., Burgio, M., Soddu, S., Bruzzaniti, V., Guerrisi, A., & Verdina, A. (2024). Cumulative Dose from Recurrent CT Scans: Exploring the DNA Damage Response in Human Non-Transformed Cells. International Journal of Molecular Sciences. 25. 7064. https://doi.org/10.3390/ijms25137064.
• [8] Wang, S., Li, G., Du, H., & Feng, J. (2024). Low-dose radiation from CT examination induces DNA double-strand breaks and detectable changes of DNA methylation in peripheral blood cells. International Journal of Radiation Biology, 100(2), 197–208. https://doi.org/10.1080/09553002.2023.2267667.
• [9] Bogdanova, NV., Jguburia, N., Ramachandran, D., Nischik, N., Stemwedel, K., Stamm, G., Werncke, T., Wacker, F., Dörk, T., Christiansen, H. (2021). Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes. Front Oncol, 11, 634389. https://doi.org/10.3389/fonc.2021.634389.
• [10] Incerti, S.; Baldacchino, G.; Bernal, M.; Capra, R.; Champion, C.; Francis, X.; Guèye, P.; Mantero, A.; Mascialino, B.; Moretto, P.; et al., (2010). The Geant4-DNA Project. International Journal of Modeling, Simulation, and Scientific Computing, 1(2), 157–178. https://doi.org/10.1142/S1793962310000122
• [11] Incerti, S.; Kyriakou, I.; Bernal, M. A.; Bordage, M. C.; Francis, Z.; Guatelli, S.; Ivanchenko, V.; Karamitros, M.; Lampe, N.; Lee, S. B.; Meylan, S.; et al., (2018) Geant4-DNA Example Applications for Track Structure Simulations in Liquid Water: A Report From The Geant4-DNA Project. Medical Physics, 45(8), e722–e739. https://doi.org/10.1002/mp.13048
• [12] Karamitros, M., Mantero, A., Incerti, S., Friedland, W., Baldacchino, G., Barberet, P., et al., (2011). Modeling radiation chemistry in the Geant4 toolkit. Progress in Nuclear Science and Technology, 2, 503-508.
• [13] Weiss, J. F., & Landauer, M. R., (2003). Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology, 189(1-2), 1-20. https://doi.org/10.1016/s0300-483x(03)00149-5
• [14] Chatzipapas, K. P.; Tran, N. H.; Dordevic, M.; Zivkovic, S.; Zein, S.; Shin, W. G.; Sakata, D.; Lampe, N.; Brown, J. M. C.; Ristic-Fira, A.; et al., (2023). Simulation of DNA Damage Using Geant4-DNA: An Overview of The “molecularDNA” Example Application. Precision Radiation Oncology, 7(1), 4–14. https://doi.org/10.1002/pro6.1186
• [15] Margis, S.; Magouni, M.; Kyriakou, I.; Georgakilas, A. G.; Incerti, S.; Emfietzoglou, D., (2020). Microdosimetric Calculations of The Direct DNA Damage Induced by Low Energy Electrons Using The Geant4-DNA Monte Carlo Code. Physics in Medicine and Biology, 65(4), 045007. https://doi.org/10.1088/1361-6560/ab6b47
• [16] Allison, J.; Amako, K.; Apostolakis, J.; Arce, P.; Asai, M.; Aso, T.; Bagli, E.; Bagulya, A.; Banerjee, S.; Barrand, G.; et al., (2016). Recent Developments in Geant4. Nuclear Instruments and Methods in Physics Research Section A., 835, 186–225. https://doi.org/10.1016/j.nima.2016.06.125
• [17] Allison, J.; Amako, K; Apostolakis, J.; Araujo, H.; Arce Dubois, P.; Asai, M.; Barrand, G.; Capra, R.; Chauvie, S.; Chytracek, R.; et al., (2006). Geant4 Developments and Applications. IEEE Transactions on Nuclear Science, 53(1), 270–278. https://doi.org/10.1109/TNS.2006.869826
• [18] Agostinelli, S.; Allison, J.; Amako, K.; Apostolakis, J.; Araujo, H.; Arce, P.; Asai, M.; Axen, D.; Banerjee, S.; Barrand, G.; et al., (2003) Geant4 A Simulation Toolkit. Nuclear Instruments and Methods in Physics Research Section A., 506, 250–303. https://doi.org/10.1016/S0168-9002(03)01368-8
• [19] Schuemann, J.; McNamara, A. L.; Warmenhoven, J. W.; Henthorn, N. T.; Kirkby, K. J; Merchant, M. J.; Ingram, S.; Paganetti, H.; Held, K. D.; Ramos-Mendez, J.; et al., (2019). A New Standard DNA Damage (SDD) Data Format. Radiation Research, 191(1), 76–92. https://doi.org/10.1667/RR15209.1
• [20] Shin, W. G.; Sakata, D.; Lampe, N.; Belov, O.; Tran, N.H.; Petrovic, I.; Ristic-Fira, A.; Dordevic, M.; Bernal, M.A.; Bordage, M.-C.; et al., (2021), A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast. Cancers, 13, 4940. https://doi.org/10.3390/cancers13194940
• [21] Chatzipapas, K. P.; Dordevicb M.; Zivkovicb, S.; Trana N. H.; Lampec, N.; Sakatad, D.; Petrovicb, I.; Ristic-Firab, A.; Shine, W. G.; Zeina, S.; et al., (2023), Geant4-DNA Simulation of Human Cancer Cells Irradiation with Helium Ion Beams. Physica Medica. 2023, 112, 102613. https://doi.org/10.1016/j.ejmp.2023.102613
• [22] Famulari, G.; Pater, P.; Enger, S. A., (2018). Microdosimetric Evaluation of Alternative High and Intermediate Energy High Dose Rate Brachytherapy Sources a Geant4-DNA Simulation Study. International Journal of Radiation Oncology, Biology, Physics, 100(1), 270–277. https://doi.org/10.1016/j.ijrobp.2017.09.040
• [23] Bernal, M. A., Bordage, M.C.; Brown, J. M. C.; Davídková, M.; Delage E.; El Bitar M.; Enger, S. A.; Francis Z.; Guatelli, S.; Ivanchenko, V. N.; et al., (2015). Track Structure Modeling in Liquid Water: A Review of The Geant4-DNA Very Low Energy Extension of The Geant4 Monte Carlo Simulation Toolkit. Physica Medica, 31(8), 861–874. https://doi.org/10.1016/j.ejmp.2015.10.087
• [24] Tran, H. N.; Archer, J; Baldacchino, G.; Brown, J. M. C.; Chappuis, F.; Cirrone, G. A. P.; Desorgher, L.; Dominguez, N.; Fattori, S.; Guatelli, S.; et al., (2024). Review of Chemical Models and Applications in Geant4-DNA: Report from the ESA BioRad III Project. Medical Physics, 51(10), 5873–5889. https://doi.org/10.1002/mp.17256
• [25] Le, T.A., Tran, H.N., Fattori, S., Phan, V.C., Incerti, S., (2024). Modeling water radiolysis with Geant4-DNA: Impact of the temporal structure of the irradiation pulse under oxygen conditions. arXiv:2409.11993, https://doi.org/10.48550/arXiv.2409.