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

Shin, Wook-Geun; Sakata, Dousatsu; Lampe, Nathanael; Belov, Oleg; Tran, Ngoc Hoang; Petrovic, Ivan; Ristic-Fira, Aleksandra; Dordevic, Milos; Bernal, Mario A.; Bordage, Marie-Claude; Francis, Ziad; Kyriakou, Ioanna; Perrot, Yann; Sasaki, Takashi; Villagrasa, Carmen; Guatelli, Susanna; Breton, Vincent; Emfietzoglou, Dimitris; Incerti, Sebastien

Simple Summary: DNA damage caused by ionizing radiation in a human fibroblast cell evaluated by the Geant4-DNA Monte Carlo toolkit is presented. A validation study using a computational geometric human DNA model was then carried out, and the calculated DNA damage as a function of particle type and energy is presented. The results of this work showed a significant improvement on past work and were consistent with recent radiobiological experimental data, such as damage yields. This work and the developed methodology could impact a broad number of research fields in which the understanding of radiation effects is crucial, such as cancer radiotherapy, space science, and medical physics. 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.

FIBROBLASTS; CARCINOGENESIS; RADIATION; ENERGY transfer; SYSTEM analysis; DNA damage

Cancers, 2021, Vol 13, Issue 19, p4940

2072-6694

Academic Journal

10.3390/cancers13194940