scholarly journals Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 35
Author(s):  
Ioanna Kyriakou ◽  
Dousatsu Sakata ◽  
Hoang Ngoc Tran ◽  
Yann Perrot ◽  
Wook-Geun Shin ◽  
...  

The Geant4-DNA low energy extension of the Geant4 Monte Carlo (MC) toolkit is a continuously evolving MC simulation code permitting mechanistic studies of cellular radiobiological effects. Geant4-DNA considers the physical, chemical, and biological stages of the action of ionizing radiation (in the form of x- and γ-ray photons, electrons and β±-rays, hadrons, α-particles, and a set of heavier ions) in living cells towards a variety of applications ranging from predicting radiotherapy outcomes to radiation protection both on earth and in space. In this work, we provide a brief, yet concise, overview of the progress that has been achieved so far concerning the different physical, physicochemical, chemical, and biological models implemented into Geant4-DNA, highlighting the latest developments. Specifically, the “dnadamage1” and “molecularDNA” applications which enable, for the first time within an open-source platform, quantitative predictions of early DNA damage in terms of single-strand-breaks (SSBs), double-strand-breaks (DSBs), and more complex clustered lesions for different DNA structures ranging from the nucleotide level to the entire genome. These developments are critically presented and discussed along with key benchmarking results. The Geant4-DNA toolkit, through its different set of models and functionalities, offers unique capabilities for elucidating the problem of radiation quality or the relative biological effectiveness (RBE) of different ionizing radiations which underlines nearly the whole spectrum of radiotherapeutic modalities, from external high-energy hadron beams to internal low-energy gamma and beta emitters that are used in brachytherapy sources and radiopharmaceuticals, respectively.

2021 ◽  
Vol 22 (15) ◽  
pp. 7879
Author(s):  
Yingxia Gao ◽  
Yi Zheng ◽  
Léon Sanche

The complex physical and chemical reactions between the large number of low-energy (0–30 eV) electrons (LEEs) released by high energy radiation interacting with genetic material can lead to the formation of various DNA lesions such as crosslinks, single strand breaks, base modifications, and cleavage, as well as double strand breaks and other cluster damages. When crosslinks and cluster damages cannot be repaired by the cell, they can cause genetic loss of information, mutations, apoptosis, and promote genomic instability. Through the efforts of many research groups in the past two decades, the study of the interaction between LEEs and DNA under different experimental conditions has unveiled some of the main mechanisms responsible for these damages. In the present review, we focus on experimental investigations in the condensed phase that range from fundamental DNA constituents to oligonucleotides, synthetic duplex DNA, and bacterial (i.e., plasmid) DNA. These targets were irradiated either with LEEs from a monoenergetic-electron or photoelectron source, as sub-monolayer, monolayer, or multilayer films and within clusters or water solutions. Each type of experiment is briefly described, and the observed DNA damages are reported, along with the proposed mechanisms. Defining the role of LEEs within the sequence of events leading to radiobiological lesions contributes to our understanding of the action of radiation on living organisms, over a wide range of initial radiation energies. Applications of the interaction of LEEs with DNA to radiotherapy are briefly summarized.


2006 ◽  
Vol 45 (12) ◽  
pp. 1893-1896 ◽  
Author(s):  
Sylwia Ptasińska ◽  
Stephan Denifl ◽  
Sascha Gohlke ◽  
Paul Scheier ◽  
Eugen Illenberger ◽  
...  

2019 ◽  
Vol 199 ◽  
pp. 01016 ◽  
Author(s):  
Jan M. Friedrich

Within the broad physics programme of the COMPASS collaboration at CERN SPS, soft reactions of high-energy hadron beams on different nuclear targets are investigated. Aiming at a better understanding of the strong interaction, novel results range from tests of chiral symmetry breaking to properties of diffractively produced meson resonances studied in their multi-particle decays, such as the a1(1420) with unusual properties. The talk will highlight the challenges of the employed experimental techniques, and as well of the analysis methods, that are developed to a large extent along with the analysis of the world’s largest data sets in the field.


2019 ◽  
Vol 21 (1) ◽  
pp. 111
Author(s):  
Kenny Ebel ◽  
Ilko Bald

The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A4), d(A8), d(A12), d(A16), and d(A20)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A4) to d(A16), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A20), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA20 sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy.


1999 ◽  
Vol 44 (8) ◽  
pp. 711-715 ◽  
Author(s):  
Yanhua Du ◽  
Shenghai Huang ◽  
Zheng Tan ◽  
Yingzhi Lin ◽  
Guanying Qiu

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