scholarly journals Impact of the Lorentz Force on Electron Track Structure and Early DNA Damage Yields in Magnetic Resonance-Guided Radiotherapy

Author(s):  
Yoshie Yachi ◽  
Takeshi Kai ◽  
Yusuke Matsuya ◽  
Yuho Hirata ◽  
Yuji Yoshii ◽  
...  

Abstract Magnetic resonance-guided radiotherapy (MRgRT) has been developed and installed in recent decades for external radiotherapy in several clinical facilities. The Lorentz force modulates dose distribution by charged particles in MRgRT; however, the impact by this force on low-energy electron track structure and early DNA damage induction remain unclear. In this study, we estimated features of electron track structure and biological effects in a static magnetic field (SMF) using a general-purpose Monte Carlo code, Particle and Heavy Ion Transport code System (PHITS) that enables us to simulate low-energy electrons down to 1 meV by track-structure mode. The macroscopic dose distributions by electrons above approximately 300 keV initial energy in liquid water are changed by both perpendicular and parallel SMFs against the incident direction, indicating that the Lorentz force plays an important role in calculating dose within tumours. Meanwhile, DNA damage estimation based on the spatial patterns of atomic interactions indicates that the initial yield of DNA double-strand breaks (DSBs) is independent of the SMF intensity. The DSB induction is predominantly attributed to the secondary electrons below a few tens of eV, which are not affected by the Lorentz force. Our simulation study suggests that treatment planning for MRgRT can be made with consideration of only changed dose distribution.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pavel Kundrát ◽  
Werner Friedland ◽  
Janine Becker ◽  
Markus Eidemüller ◽  
Andrea Ottolenghi ◽  
...  

Abstract Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.


2016 ◽  
Vol 119 (19) ◽  
pp. 194902 ◽  
Author(s):  
I. Kyriakou ◽  
M. Šefl ◽  
V. Nourry ◽  
S. Incerti

2021 ◽  
Author(s):  
Fabiana Da Pieve ◽  
Bin Gu ◽  
Natalia Koval ◽  
Daniel Muñoz Santiburcio ◽  
Jos Teunissen ◽  
...  

<p>Cosmic Rays, in particular the high charge and high energy (HZE) particles and eventual secondary low energy protons, are high Linear Energy Transfer (LET) radiation, i.e. they transfer a high amount of energy to the target per unit path length travelled in the target itself, leaving behind a dense track of ionization and atomic excitations. Understanding the radiation physics and the biology induced by the impact of high LET radiation is of importance for different fields of research, such as radiation therapy with charged particles, space radiation protection of astronauts and of human explorers on Mars and eventually also survival of any bacterial, plant cell on other planetary/small bodies. While data for low LET radiation  such as X-ray have been studied in the survivors of the atomic-bombs, medical patients and nuclear reactor workers, for high LET radiation there is no relevant collection of human data for risk estimates, and experiments with nuclei created at accelerators are necessary.</p><p>At present we still do not have an understanding of how the  radiation  interaction  with a  single nanometric  target (units of DNA), the so-called track  structure [1],  should  decide  the  fate  of  the  irradiated cell. Monte Carlo (MC) track structure codes essentially work only with the physics given by impact cross sections on the sole water, there is no real consideration of the electronic/chemical characteristics of the hosted biomolecule [2]. Limitations given by such an approach have been highlighted [3], but on the positive side a massive effort is being done to follow the different steps of radiation effects up to biological damage [4].</p><p>In this contribution we would like to highlight how a chain of models from different communities could be of help to study the radiation effects on biomolecules. In particular, we will present how ab-initio (parameter-free) approaches from the chemical-physics community can be used to derive in detail the energy loss of the impacting ions/secondary electrons on water and small biological units [5,6], either following in real time the ion or based on perturbative theories for low energy electrons, and how the derived quantity can be given  as input to Monte Carlo track structure codes, extending their capabilities to different relevant targets. Given the physical limitations and high costs of irradiation experiments, such calculations offer an efficient approach that can boost the understanding of radiation physics and consolidate existing MC track structure codes.</p><p>This work is initiated in the context of the EU H2020 project ESC2RAD, Grant 776410.</p><p>[1] H. Nikjoo, S. Uehara, W.E. Wilson, et al, International Journal of Radiation Biology 73, 355 (1998)</p><p>[2] H. Palmans, H Rabus, A L Belchior, et al, Br. J. Radiol. 88, 20140392 (2015)</p><p>[3] H. Rabus and H. Nettelback, Radiation Measurements 46, 1522 (2011)</p><p>[4] M. Karamitros, S. Luan, M.A. Bernal, et al,  Journal of Computational Physics 274,  841 (2014)</p><p>[5] B. Gu, B. Cunningham D. Munoz-Santiburcio, F. Da Pieve, E. Artacho and J. Kohanoff, J. Chem. Phys. 153, 034113 (2020)</p><p>[6] N. Koval, J. Kohanoff, E. Artacho et al, in preparation</p>


2004 ◽  
Vol 161 (5) ◽  
pp. 591-596 ◽  
Author(s):  
W. E. Wilson ◽  
J. H. Miller ◽  
D. J. Lynch ◽  
R. R. Lewis ◽  
M. Batdorf

2020 ◽  
Vol 65 (4) ◽  
pp. 045007 ◽  
Author(s):  
Stefanos Margis ◽  
Maria Magouni ◽  
Ioanna Kyriakou ◽  
Alexandros G Georgakilas ◽  
Sebastien Incerti ◽  
...  

2020 ◽  
Vol 21 (5) ◽  
pp. 1701 ◽  
Author(s):  
Yusuke Matsuya ◽  
Toshiaki Nakano ◽  
Takeshi Kai ◽  
Naoya Shikazono ◽  
Ken Akamatsu ◽  
...  

Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.


2021 ◽  
Vol 11 ◽  
Author(s):  
Catherine M. Nickson ◽  
Maria Rita Fabbrizi ◽  
Rachel J. Carter ◽  
Jonathan R. Hughes ◽  
Andrzej Kacperek ◽  
...  

Ionizing radiation (IR) principally acts through induction of DNA damage that promotes cell death, although the biological effects of IR are more broad ranging. In fact, the impact of IR of higher-linear energy transfer (LET) on cell biology is generally not well understood. Critically, therefore, the cellular enzymes and mechanisms responsible for enhancing cell survival following high-LET IR are unclear. To this effect, we have recently performed siRNA screening to identify deubiquitylating enzymes that control cell survival specifically in response to high-LET α-particles and protons, in comparison to low-LET X-rays and protons. From this screening, we have now thoroughly validated that depletion of the ubiquitin-specific protease 9X (USP9X) in HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells using small interfering RNA (siRNA), leads to significantly decreased survival of cells after high-LET radiation. We consequently investigated the mechanism through which this occurs, and demonstrate that an absence of USP9X has no impact on DNA damage repair post-irradiation nor on apoptosis, autophagy, or senescence. We discovered that USP9X is required to stabilize key proteins (CEP55 and CEP131) involved in centrosome and cilia formation and plays an important role in controlling pericentrin-rich foci, particularly in response to high-LET protons. This was also confirmed directly by demonstrating that depletion of CEP55/CEP131 led to both enhanced radiosensitivity of cells to high-LET protons and amplification of pericentrin-rich foci. Our evidence supports the importance of USP9X in maintaining centrosome function and biogenesis and which is crucial particularly in the cellular response to high-LET radiation.


2021 ◽  
Vol 9 ◽  
Author(s):  
Pavel Kundrát ◽  
Werner Friedland ◽  
Andrea Ottolenghi ◽  
Giorgio Baiocco

Existing radiation codes for biomedical applications face the challenge of dealing with largely different spatial scales, from nanometer scales governing individual energy deposits to macroscopic scales of dose distributions in organs and tissues in radiotherapy. Event-by-event track-structure codes are needed to model energy deposition patterns at cellular and subcellular levels. In conjunction with DNA and chromatin models, they predict radiation-induced DNA damage and subsequent biological effects. Describing larger-scale effects is the realm of radiation transport codes and dose calculation algorithms. A coupling approach with a great potential consists in implementing into radiation transport codes the results of track-structure simulations captured by analytical formulas. This strategy allows extending existing transport codes to biologically relevant endpoints, without the need of developing dedicated modules and running new computationally expensive simulations. Depending on the codes used and questions addressed, alternative strategies can be adopted, reproducing DNA damage in dependence on different parameters extracted from the transport code, e.g., microdosimetric quantities, average linear energy transfer (LET), or particle energy. Recently, a comprehensive database on DNA damage induced by ions from hydrogen to neon, at energies from 0.5 GeV/u down to their stopping, has been created with PARTRAC biophysical simulations. The results have been captured as a function of average LET in the cell nucleus. However, the formulas are not applicable to slow particles beyond the Bragg peak, since these can have the same LET as faster particles but in narrower tracks, thus inducing different DNA damage patterns. Particle energy distinguishes these two cases. It is also more readily available than LET from some transport codes. Therefore, a set of new analytical functions are provided, describing how DNA damage depends on particle energy. The results complement the analysis of the PARTRAC database, widening its potential of application and use for implementation in transport codes.


Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiangbin Wei ◽  
Qiwu Shi ◽  
Lidan Xiong ◽  
Guang Xin ◽  
Tao Yi ◽  
...  

AbstractThe experiment of inertial confinement fusion by the “ShengGuang (SG)-III” prototype laser facility is a transient and extreme reaction process within several nanoseconds, which could form a very complicated and intense electromagnetic field around the target chamber of the facility and may lead to harmful effect on people around. In particular, the biological effects arising from such specific environment field could hardly be ignored and have never been investigated yet, and thus, we reported on the investigation of the biological effects of radiation on HaCat cells and PC12 cells to preliminarily assess the biological safety of the target range of the "SG-III" prototype laser facility. The viability revealed that the damage of cells was dose-dependent. Then we compared the transcriptomes of exposed and unexposed PC12 cells by RNA-Seq analysis based on Illumina Novaseq 6000 platform and found that most significantly differentially expressed genes with corresponding Gene Ontology terms and pathways were strongly involved in proliferation, transformation, necrosis, inflammation response, apoptosis and DNA damage. Furthermore, we find increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that pathways or mechanisms regarding DNA damage repair was are quickly activated. It was found that "SG-III" prototype radiation could induce DNA damage and promote apoptotic necrosis.


Sign in / Sign up

Export Citation Format

Share Document