Investigating ultra-high dose rate water radiolysis using the Geant4-DNA toolkit and a Geant4 model of the Oriatron eRT6 electron linac.

Ultra-high dose rate FLASH radiotherapy, a promising cancer treatment approach, offers the potential to reduce healthy tissue damage during radiotherapy. As the mechanisms underlying this process remain unknown, several hypotheses have been proposed, including the altered production of radio-induced species under ultra-high dose rate (UHDR) conditions. This study explores realistic irradiation scenarios with various dose-per-pulse and investigates the role of pulse temporal structure.

Development of a novel computational technique to create DNA and cell geometrical models for Geant4-DNA.

Background: This study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve.

Methods: A Python-based tool named "complexDNA" was developed to facilitate the design of both simple and complex DNA geometries.

Quantitative analysis of dose dependent DNA fragmentation in dry pBR322 plasmid using long read sequencing and Monte Carlo simulations.

Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose-effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences.

Monte Carlo simulations of microdosimetry and radiolytic species production at long time post proton irradiation using GATE and Geant4-DNA.

Background: Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments.

In-silico calculations of DNA damage induced by α-particles in the Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment.

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.

The general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension to investigate mechanisms underlying the FLASH effect in radiotherapy: Current status and challenges.

FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown.

Modeling of scavenging systems in water radiolysis with Geant4-DNA.

Purpose: This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of HO following a Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons.

Methods: To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers.

Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory.

Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations.

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

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.

Geant4-DNA Modeling of Water Radiolysis beyond the Microsecond: An On-Lattice Stochastic Approach.

In this work, we use the next sub-volume method (NSM) to investigate the possibility of using the compartment-based ("on-lattice") model to simulate water radiolysis. We, first, start with a brief description of the reaction-diffusion master equation (RDME) in a spatially discretized simulation volume ("mesh"), which is divided into sub-volumes (or "voxels"). We then discuss the choice of voxel size and merging technique of a given mesh, along with the evolution of the system using the hierarchical algorithm for the RDME ("hRDME").

Assessment of DNA damage with an adapted independent reaction time approach implemented in Geant4-DNA for the simulation of diffusion-controlled reactions between radio-induced reactive species and a chromatin fiber.

Purpose: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA.

Methods: This new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background And Objectives: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.