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. 2021 Sep 30;13(19):4940.
doi: 10.3390/cancers13194940.

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

Wook-Geun Shin  1   2   3 , Dousatsu Sakata  4 , Nathanael Lampe  5 , Oleg Belov  6   7 , Ngoc Hoang Tran  1 , Ivan Petrovic  8 , Aleksandra Ristic-Fira  8 , Milos Dordevic  8 , Mario A Bernal  9 , Marie-Claude Bordage  10   11 , Ziad Francis  12 , Ioanna Kyriakou  13 , Yann Perrot  14 , Takashi Sasaki  15 , Carmen Villagrasa  14 , Susanna Guatelli  16 , Vincent Breton  17 , Dimitris Emfietzoglou  13 , Sebastien Incerti  1
Affiliations

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

Wook-Geun Shin et al. Cancers (Basel). .

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.

Keywords: DNA damage; Geant4-DNA; Monte Carlo track structure simulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Schematic illustration of the molecular structure of the DNA double helix. The spheres represent adenine (C5H5N5, blue), thymine (C5H6N2O2, magenta), guanine (C5H5N5O, green), cytosine (C4H5N3O, cyan), sugar (C5H10O4, deoxyribose, red), and phosphate (H3PO4, yellow), respectively. (b) Simplified chromatin fiber segments (straight and turned) and a unit of Hilbert curve. (c) The modeled fibroblast cell nucleus.
Figure 2
Figure 2
A schematic illustration of the geometrical configuration of the human cell nucleus and source term. Figures adapted from [15].
Figure 3
Figure 3
The number of total strand breaks as a function of LET calculated by Geant4-DNA (this work, [15,16]) and PARTRAC [23].
Figure 4
Figure 4
The SSB (left upper) and DSB yields (right upper), and SSB/DSB ratio (left below) as a function of LET for the MCTS simulations and measurements.
Figure 5
Figure 5
Histogram of the fragment length distribution after 100 Gy irradiation with 1 MeV protons. Simulations (lines) and measurements (symbols) are shown.
Figure 6
Figure 6
Protectable damage fraction, which is the ratio of protectable DSBs over the total number of DSBs, as a function of LET. Geant4-DNA simulations and measurements are shown.
Figure 7
Figure 7
The γ-H2AX yield as a function of repair time from irradiation by 137Cs at a dose of 1 Gy. The calculated repair model in this study was compared with the calculations of Belov et al. (2015) [62], Sakata et al. (2020) [15], and the experimental data of Asaithamby et al. (2008) [38].
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