Ion beams have been widely applied in a few biological research fields such as radioactive breeding, health protection, and tumor therapy. Up to now many interesting and impressive achievements in biology and agriculture have been made. Over the past several decades, scientists in biology, physics, and chemistry have pursued investigations focused on understanding the mechanisms of these radiobiological effects of ion beams. From the chemical point of view, these effects are due to the ion irradiation induced biomolecular damage, direct or indirect. In this review, we will present a chemical overview of the direct effects of ion irradiation upon DNA and its components, based on a review of literature combined with recent experimental results. It is suggested that, under ion bombardment, a DNA molecule undergoes a variety of processes, including radical formation, atomic displacement, intramolecular bond-scissions, emission of fragments, fragment recombination and molecular crosslink, which may lead to genetic mutations or cell death. This may help to understand the mechanisms of the radiobiological effects caused by ion irradiation, such as radiation breeding and tumor therapy.
$TiO_{2}$ nanoparticles (NPs) are widely used in the environmental engineering, medicine, chemical and food industries due to their unique photocatalytic and biocidal properties. NPs may generate reactive oxygen species and, hence, have the toxic effect on the living cells via oxidative stress. An external UV irradiation may magnify the photocatalytic properties of $TiO_{2}$ NPs. In this regard, we have analyzed the influence of $TiO_{2}$ NPs on the conformation and thermal stability of native DNA in a buffer solution without and under UV irradiation exploiting absorption spectroscopy with DNA…
Abnormalities within cells result in nanoscale structural alterations can be characterized via confocal imaging and quantification of these alterations. Accidental or deliberate exposure to total body irradiation (TBI) have adverse effects on the nuclear DNAs of cells. Here, we study the DNA molecular mass density spatial structural alterations of chromatin in cell nuclei of gut tissues caused by the exposure to standard doses of 4Gy TBI, using the light localization technique called inverse participation ratio (IPR) in confocal images. Results indicate radiation suppresses DNA spatial mass de…
Due to the physical and chemical processes that are involved, interactions of ionizing radiations with cells lead to single- and double-strand breaks (SSB and DSB) and base damage to DNA cells. The damage may kill the cells or may be mis-repaired and lead to genetic diseases and cancers. Track structure Monte Carlo simulation of the DNA damage provides types of the damage and their frequencies. In the present work, to derive initial DNA damage, we used the Geant4-DNA code to simulate the physical, physico-chemical and chemical stages of interactions of incident beams of 100 eV to 4.5 keV elect…
In this work, we report a novel strategy to construct molecular diodes with a record tunable rectification ratio of as high as 10^6 using oxidatively damaged DNA molecules. Being exposed to several endogenous and exogenous events, DNA suffers constant oxidative damages leading to oxidation of guanine to 8-Oxoguanine (8oxoG). Here, we study the charge migration properties of native and oxidatively damaged DNA using a multiscale multiconfigurational methodology comprising of molecular dynamics, density functional theory and kinetic Monte Carlo simulations. We perform a comprehensive study to und…
The scientific community shows a great interest in the study of DNA damage induction, DNA damage repair and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in-silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named "molecularDNA", publicly released in the 11.1 version of Geant4 (December 2022). It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example currently proposes …
The interaction of heavy charged particles with DNA is of interest for several areas, from hadrontherapy to aero-space industry. In this paper, a TD-DFT study on the interaction of a 4 keV proton with an isolated DNA base pair was carried out. Ehrenfest dynamics was used to study the evolution of the system during and after the proton impact up to about 193 fs. This time was long enough to observe the dissociation of the target, which occurs between 80-100 fs. The effect of base pair linking to the DNA double helix was emulated by fixing the four O3' atoms responsible for the attachment. The b…
In order to study the molecular damage induced in the form of single-strand and double-strand breaks by the ionizing radiation at the DNA level, Geant4-DNA Monte Carlo simulation code for complete transportation of primary protons and other secondary particles in liquid water have been employed in this work. To this aim, a B-DNA model and a thorough classification of DNA damage concerning their complexity were used. Strand breaks were assumed to have been primarily originated by direct physical interactions via energy depositions, assuming a threshold energy of 17.5 eV, or indirect chemical re…
The oxidative damage of DNA is a compelling issue in molecular biophysics as it plays a vital role in the epigenetic control of gene expression and is believed to be associated with mutagenesis, carcinogenesis, and ageing. To understand the microscopic structural changes in physical properties of DNA and the resulting influence on its function due to oxidative damage of its nucleotide bases, we have conducted all-atom molecular dynamic simulations of double-stranded DNA (dsDNA) with its guanine bases being oxidized. The guanine bases are more prone to oxidative damage due to the lowest value o…
In the present work, we develop a general spatial stochastic model to describe the formation and repair of radiation-induced DNA damage. The model is described mathematically as a measure-valued particle-based stochastic system and extends in several directions the model developed in Cordoni et.al. 2021, Cordoni et.al. 2022a, Cordoni et.al. 2022b. In this new spatial formulation, radiation-induced DNA damage in the cell nucleus can undergo different pathways to either repair or lead to cell inactivation. The main novelty of the work is to rigorously define a spatial model that considers the pa…
{\bf Purpose}: To develop a first principle and multi-scale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nano-scale radio-chemical to macro-scale cell biological pathways, spanning from initial DNA damage to tissue late effects. {\bf Methods}: The method is combination of analytical and multi-scale computational steps including (1) derivation of functional dependencies of NTCP on DNA driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (2) 3D-surface…
Ion-induced DNA damage is an important effect underlying ion-beam cancer therapy. This paper introduces the methodology of modeling DNA damage induced by a shock wave caused by a projectile ion. Specifically, it is demonstrated how single- and double-strand breaks in a DNA molecule could be described by the reactive CHARMM (rCHARMM) force field implemented in the program MBN Explorer. The entire workflow of performing the shock wave simulations, including obtaining the crucial simulation parameters, is described in seven steps. Two exemplary analyses are provided for a case study simulation se…
After irradiation of cancer cells in the ion beam therapy method the concentration of hydrogen peroxide in the cell medium grows significantly. But the role of hydrogen peroxide molecules in cancer treatment has not been determined yet. We assume that interaction of peroxide molecules with DNA atomic groups can block the genetic information of the cancer cell and lead to its neutralization. To understand the possibility of DNA deactivation in the cell, in the present study the formation of complexes of hydrogen peroxide molecules with DNA specific recognition sites (nucleic bases) is considere…
The radiation-induced damages in bio-molecules are ubiquitous processes in radiotherapy, radio-biology and critical to space-projects. In this study we present a precise quantification of the fragmentation mechanisms of deoxyribonucleic acid (DNA) and the molecules surrounding DNA such as oxygen and water under non-equilibrium conditions using the first-principle calculations based on density functional theory (DFT). Our results reveal the structural stability of DNA-bases and backbone that withstand up to a combined threshold of charge and hydrogen abstraction owing to simultaneous direct and…
Impact of Oxygen on DNA Damage Distribution in 3D Genome and its Correlation to Oxygen Enhancement Ratio after High-LET Irradiation
Department of Engineering Physics, Tsinghua University（清华大学工程物理系）；Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education（教育部粒子与辐射成像重点实验室）；Institute of Fluid Physics, China Academy of Engineering Physics（中国工程物理研究院流体物理研究所）
