Calculation of direct and indirect damages of Auger electron-emitting radionuclides based on the atomic geometric model: A simulation study using Geant4-DNA toolkit

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Abstract

This study represents the detailed calculation of damage by Auger electrons of radionuclides 99mTc,111In,125I and 123I to DNA molecules at cellular scales, using Geant4-DNA toolkit. The average number of breaks in DNA are shown as a function of distance from the center of the DNA axis to position of Auger electron decay and compared with results obtained for different models of DNA used by others. The highest damage occurs for electrons with energies below 1 keV, and in proximity of DNA molecule. The calculation of DSB yield per Gy per Dalton is carried out for above radionuclides. The most considerable damage occurs when the distance between an Auger electron-emitting atom and DNA is about 2.5 nm, and 50% decreases happen when the distance is about 3.5 to 4 nm. DSB yield are comparable with other experimental and simulation data, and show a good agreement between our results and other works.

Introduction

When living tissue is exposed to ionizing radiation, some biological effects may be produced as a result of energy deposition within a nucleus of a living cell or further damage the DNA [1]. DNA is a large molecule, consists of two long strands. Radiation interaction with DNA, especially by the presence of short-range Auger electrons that bears a high local Linear Energy Transfer (LET), may cause severe breaks to these strands and can control the speed of growths of the cancerous cells. This effect is a direct effect on tissue’s cellular by ionizing radiation. Also, the radiation may produce free radicals when interacting with other atoms or molecules, which is considered an indirect effect. The essential effect caused by radio-induced Auger electrons is single-strand breaks (SSB) and double-strand breaks (DSB) [2], [3], [4], [5], [6], [7]. When two SSB are in two opposite strands and are separated by 10 base pairs or more, one DSB occurs (Fig. 1) [7], [8], [9]. The high radiotoxicity of Auger electron-emitting radionuclides has been the topic of discussion in targeted therapy of cancers. Many low energy electrons in nanometer ranges are created. This low energy electrons deposit their energy within 1 to 2 nm of their decay positions.

Strand breaks may be produced, when ionizing radiation’s energy is deposited within the chromosomes [10]. Due to the high toxicity and short-range of Auger electron and minimum irradiation of critical organs, they are good candidates for cancer treatment. Auger electron-emitting Radiopharmaceuticals such as 125I,111In,123I, and 99mTc are used widely in diagnostic imaging and therapy oncology. Recently, interest in radionuclide therapy or targeted radiotherapy, particularly for patients with inoperable or multi-site disease as neuroendocrine tumors and disseminated bone metastases, are caused to use them. The use of radionuclides provides an alternative to surgery or medical treatments in cancer. It has the potential to eradicate tumor cells and small metastases and is a useful complement or alternative to chemotherapy. Auger electron-emitting radionuclides with high LET and short-range expand the usefulness of radiation techniques to successful treatment in small cells or metastases in cancer [11]. More recently, new radiotherapy treatments demand theoretical determination of radiation track structure at the nanoscale and the radiation damage at the cellular and subcellular levels on DNA molecules. In targeted a with Auger electron radionuclides, the calculation of energy deposition at the cellular and subcellular level is carried out for short path lengths and high LET of particles emitted by the radionuclides on the small target volumes. Damage due to radiation has been investigated using theoretical and experimental methods [4], [7], [8], [12], [13], [14], [15]. Many quantitative aspects of damage have not yet been thoroughly investigated by experimental methods, where simulation helps the understanding of some details of induced effects by ionizing radiation in cellular and subcellular scales. The most practical track’s structure Monte Carlo codes for Simulations are PARTRAC [16], [17], PITS [18], TRAX [19], RITRACKS [20], and KURBUC [21]. Geant4 is a software toolkit for the simulation of particle tracking through matters. It applies to a vast area of different fields, such as projects, including high energy particles, astrophysics, and medical physics [22]. The success of the Geant4 code resulted from insights that the micro and nanoscale model of radiation track and associated energy deposition has an essential role in the determination of the probability of formation of biological lesions. The Geant4-DNA, which is an extension of Geant4, is suitable for simulation of ionizing radiation damage at the DNA scale. It was developed in 2008. It has been extended for particle interactions with liquid water down to the eV in energy [23], [24], [25], [26], [27], [28], [29], [30]. This code can simulate the range of energies from eV to MeV.

Section snippets

Materials and methods

Geometry and Tracking of a software package based on the Monte Carlo method are designed to simulate and transport particles in the materials. The whole sample of this software package written based on the object-oriented C++ programming language is provided free by CERN in 1998 [31]. This code is supported by a large group of scientists and engineers to enhance its application and scope on biological nanometer scale damage in biophysics for several particles and a wide range of energies. The

Simulation of direct DNA damage

By presenting the atomic spectrum of radionuclides into the code, the possible damage of each energy regarding its range and position of interactions respect to the center of chromosome model will be investigated using the following conditions. If the amount of interacting energy is to be more than the energy of the threshold for direct break (10.79 eV lowest ionization energy of water in Geant4 code), a single-strand break occurs (SSB) [36]. If the interaction energies are above the threshold

Simulation of indirect DNA damage

Since the major part of the cells consists of about 70% water, when the cell is exposed to ionizing radiation, more radiation energies are absorbed by the water molecules resulting in the production of free radicals. Because free radicals are capable of spreading far enough distance, and their high chemical reaction can result in DNA damage. These effects are known as indirect effects of ionizing radiation. In the chemical stage, chemical species are OH (Hydroxyl radical),eaq,H2O2, H. Among

Results and discussion

The average number of single-strand breaks (SSBs) induced by Auger electron per decay as a function of distance from DNA central axis is shown for 99mTc,111In,125I and 123I in Fig. 2. Also, the average number of double-strand breaks (DSBs) induced by Auger electron per decay as a function of distance from DNA central axis is shown for 99mTc,111In,125I, and 123I in Fig. 3. Also, the number of SSBs and DSBs in various energies ranges are given in Fig. 4, Fig. 5 for 99mTc,111In,125Iand 123I. Table

Conclusions

The present work represents the first attempt to extend our detailed calculations of Auger electron from direct to indirect biological effect by radionuclides 99mTc,111In,125I and 123I using the Geant4-DNA model (pdb4dna). In this study, the effect of these radionuclides atoms versus the distance from the DNA central axis and versus the Auger electron energy for direct and indirect production of DSBs and SSBs are investigated. This study indicates that DSB and SSB decrease exponentially.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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