Coupling Radiation Transport and Track-Structure Simulations: Strategy Based on Analytical Formulas Representing DNA Damage Yields

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.

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Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Scientific Reports ◽

10.1038/s41598-020-72857-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Pavel Kundrát ◽

Werner Friedland ◽

Janine Becker ◽

Markus Eidemüller ◽

Andrea Ottolenghi ◽

...

Keyword(s):

Dna Damage ◽

Radiation Transport ◽

Biological Effects ◽

Spatial Scales ◽

Track Structure ◽

Monte Carlo Code ◽

Strand Breaks ◽

Light Ions ◽

Analytical Formulas ◽

Mixed Radiation Field

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.

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

10.21203/rs.3.rs-1248701/v1 ◽

2022 ◽

Author(s):

Yoshie Yachi ◽

Takeshi Kai ◽

Yusuke Matsuya ◽

Yuho Hirata ◽

Yuji Yoshii ◽

...

Keyword(s):

Dna Damage ◽

Magnetic Resonance ◽

Lorentz Force ◽

Dose Distribution ◽

Biological Effects ◽

Low Energy ◽

Track Structure ◽

Monte Carlo Code ◽

Electron Track ◽

The Impact

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.

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Transcriptome profiling of cells exposed to particular and intense electromagnetic radiation emitted by the "SG-III" prototype laser facility

Scientific Reports ◽

10.1038/s41598-021-81642-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jiangbin Wei ◽

Qiwu Shi ◽

Lidan Xiong ◽

Guang Xin ◽

Tao Yi ◽

...

Keyword(s):

Dna Damage ◽

Pc12 Cells ◽

Inertial Confinement Fusion ◽

Biological Effects ◽

Harmful Effect ◽

Transcriptome Profiling ◽

Target Chamber ◽

Target Range ◽

Inertial Confinement ◽

Laser Facility

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.

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In Vivo and In Vitro Assays Evaluating the Biological Activity of Taurine, Glucose and Energetic Beverages

Molecules ◽

10.3390/molecules26082198 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2198

Author(s):

Marcos Mateo-Fernández ◽

Fernando Valenzuela-Gómez ◽

Rafael Font ◽

Mercedes Del Río-Celestino ◽

Tania Merinas-Amo ◽

...

Keyword(s):

Dna Damage ◽

Drosophila Melanogaster ◽

Biological Activity ◽

Biological Effects ◽

Methylation Status ◽

Repetitive Sequences ◽

Energy Drinks ◽

Red Bull

Taurine is one of the main ingredients used in energy drinks which are highly consumed in adolescents for their sugary taste and stimulating effect. With energy drinks becoming a worldwide phenomenon, the biological effects of these beverages must be evaluated in order to fully comprehend the potential impact of these products on the health due to the fact nutrition is closely related to science since the population consumes food to prevent certain diseases. Therefore, the aim of this study was to evaluate the biological effects of taurine, glucose, classic Red Bull® and sugar-free Red Bull® in order to check the food safety and the nutraceutical potential of these compounds, characterising different endpoints: (i) Toxicology, antitoxicology, genotoxicology and life expectancy assays were performed in the Drosophila melanogaster model organism; (ii) The in vitro chemopreventive activity of testing compounds was determined by assessing their cytotoxicity, the proapoptotic DNA-damage capability to induce internucleosomal fragmentation, the strand breaks activity and the modulator role on the methylation status of genomic repetitive sequences of HL-60 promyelocytic cells. Whereas none tested compounds showed toxic or genotoxic effect, all tested compounds exerted antitoxic and antigenotoxic activity in Drosophila. Glucose, classic Red Bull® and sugar-free Red Bull® were cytotoxic in HL-60 cell line. Classic Red Bull® induced DNA internucleosomal fragmentation although none of them exhibited DNA damage on human leukaemia cells. In conclusion, the tested compounds are safe on Drosophila melanogaster and classic Red Bull® could overall possess nutraceutical potential in the in vivo and in vitro model used in this study. Besides, taurine could holistically be one of the bioactive compounds responsible for the biological activity of classic Red Bull®.

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