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      Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

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          Abstract

          Ionizing radiation is a common tool in medical procedures. Monte Carlo (MC) techniques are widely used when dosimetry is the matter of investigation. The scientific community has invested, over the last 20 years, a lot of effort into improving the knowledge of radiation biology. The present article aims to summarize the understanding of the field of DNA damage response (DDR) to ionizing radiation by providing an overview on MC simulation studies that try to explain several aspects of radiation biology. The need for accurate techniques for the quantification of DNA damage is crucial, as it becomes a clinical need to evaluate the outcome of various applications including both low- and high-energy radiation medical procedures. Understanding DNA repair processes would improve radiation therapy procedures. Monte Carlo simulations are a promising tool in radiobiology studies, as there are clear prospects for more advanced tools that could be used in multidisciplinary studies, in the fields of physics, medicine, biology and chemistry. Still, lot of effort is needed to evolve MC simulation tools and apply them in multiscale studies starting from small DNA segments and reaching a population of cells.

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          Most cited references171

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          The Monte Carlo Method

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            The non-Watson-Crick base pairs and their associated isostericity matrices.

            RNA molecules exhibit complex structures in which a large fraction of the bases engage in non-Watson-Crick base pairing, forming motifs that mediate long-range RNA-RNA interactions and create binding sites for proteins and small molecule ligands. The rapidly growing number of three-dimensional RNA structures at atomic resolution requires that databases contain the annotation of such base pairs. An unambiguous and descriptive nomenclature was proposed recently in which RNA base pairs were classified by the base edges participating in the interaction (Watson-Crick, Hoogsteen/CH or sugar edge) and the orientation of the glycosidic bonds relative to the hydrogen bonds (cis or trans). Twelve basic geometric families were identified and all 12 have been observed in crystal structures. For each base pairing family, we present here the 4 x 4 'isostericity matrices' summarizing the geometric relationships between the 16 pairwise combinations of the four standard bases, A, C, G and U. Whenever available, a representative example of each observed base pair from X-ray crystal structures (3.0 A resolution or better) is provided or, otherwise, theoretically plausible models. This format makes apparent the recurrent geometric patterns that are observed and helps identify isosteric pairs that co-vary or interchange in sequences of homologous molecules while maintaining conserved three-dimensional motifs.
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              Mechanisms of free radical-induced damage to DNA.

              Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5'-cyclopurine-2'-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                26 March 2020
                April 2020
                : 12
                : 4
                : 799
                Affiliations
                [1 ]3dmi Research Group, Department of Medical Physics, School of Medicine, University of Patras, 26504 Rion, Greece; kwnchatz@ 123456upatras.gr
                [2 ]Bioemission Technology Solutions (BIOEMTECH), 11472 Athens, Greece; panpap@ 123456bioemtech.com
                [3 ]Department of Medical Physics, School of Medicine, University of Ioannina, 45500 Ioannina, Greece; demfietz@ 123456gmail.com
                [4 ]DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 15780 Athens, Greece; spyrcals@ 123456gmail.com (S.A.K.); alexg@ 123456mail.ntua.gr (A.G.G.)
                [5 ]Radiation Institute for Science & Engineering, Prairie View A&M University, Prairie View, TX 77446, USA; mehada@ 123456pvamu.edu
                Author notes
                [* ]Correspondence: gkagad@ 123456gmail.com ; Tel.: +30-2610-962345
                Author information
                https://orcid.org/0000-0003-4006-9304
                https://orcid.org/0000-0002-8523-9111
                https://orcid.org/0000-0002-5971-0010
                Article
                cancers-12-00799
                10.3390/cancers12040799
                7226293
                32225023
                792c044d-e042-4bf3-a100-e61572f47d6d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 February 2020
                : 25 March 2020
                Categories
                Review

                radiobiology,nanoscale simulations,monte carlo method,ionizing radiation,complex dna damage,biological response

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