Luminal progenitor and mature cells are more susceptible than basal cells to radiation-induced DNA double-strand breaks in rat mammary tissue.

Ionizing radiation promotes mammary carcinogenesis. Induction of DNA double-strand breaks (DSBs) is the initial event after radiation exposure, which can potentially lead to carcinogenesis, but the dynamics of DSB induction and repair are not well understood at the tissue level. In this study, we used female rats, which have been recognized as a useful experimental model for studying radiation effects on the mammary gland.

Nature of the physicochemical process in water photolysis uncovered by a computer simulation.

In this work, we investigate the physicochemical process of water photolysis to bridge physical and chemical processes by a newly developed first-principles calculation code. The deceleration, thermalization, delocalization, and initial hydration of the extremely low-energy electrons ejected by water photolysis are sequentially tracked in the condensed phase. We show herein the calculated results for these sequential phenomena during 300 fs.

No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields.

The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research.

and its ingredient biopterin glucoside improved insulin sensitivity in non-alcoholic steatohepatitis model.

Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported effectively prevented non-alcoholic steatohepatitis progression in our model rats.

Spatially Fractionated Microbeam Analysis of Tissue-sparing Effect for Spermatogenesis.

Spatially fractionated radiation therapy (SFRT) has been based on the delivery of a single high-dose fraction to a large treatment area that has been divided into several smaller fields, reducing the overall toxicity and adverse effects. Complementary microbeam studies have also shown an effective tissue-sparing effect (TSE) in various tissue types and species after spatially fractionated irradiation at the microscale level; however, the underlying biological mechanism remains elusive. In the current study, using the combination of an ex vivo mouse spermatogenesis model and high-precision X-ray microbeams, we revealed the significant TSE for maintaining spermatogenesis after spatially fractionated microbeam irradiation.

The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy.

Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects.

High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation.

Microbeam radiotherapy (MRT) is based on a spatial fractionation of synchrotron X-ray microbeams at the microscale level. Although the tissue-sparing effect (TSE) in response to non-uniform radiation fields was recognized more than one century ago, the TSE of MRT in the testes and its clinical importance for preventing male fertility remain to be determined. In this study, using the combination of MRT techniques and a unique ex vivo testes organ culture, we show, for the first time, the MRT-mediated TSE for the preservation of spermatogenesis.

Application of an Ex Vivo Tissue Model to Investigate Radiobiological Effects on Spermatogenesis.

The formation of sperm by the testes through the process of spermatogenesis is highly radiosensitive and can be affected by environmental, occupational and therapeutic radiation exposures. In this study, we applied an ex vivo mouse testis organ culture as an experimental model of spermatogenesis to investigate the radiobiological effects and to demonstrate its feasibility as a tool to determine response to complex, modulated radiation fields. This model uses Acr-GFP transgenic mice, which express the marker green fluorescent proteins specific for meiosis to allow observation of functional changes in real-time that can be used to analyze radiation-induced changes in the process of spermatogenesis.

A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage.

Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code. The primary incident (1 keV) electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp) and generate secondary electrons which show non-Gaussian and non-thermal equilibrium distributions within 300 fs.

Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism.

To clarify the formation of radiation damage in DNA, the dynamic behavior of low-energy secondary electrons produced by ionizing radiation in water was studied by using a dynamic Monte Carlo code that considers the Coulombic force between electrons and their parent cations. The calculated time evolution of the mean energy, total track length, and mean traveling distance of the electrons indicated that the prehydration of the electrons occurs competitively with thermalization on a time scale of hundreds of femtoseconds. The decelerating electrons are gradually attracted to their parent cations by Coulombic force within hundreds of femtoseconds, and finally about 12.

Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context.

Purpose: To simulate the deceleration processes of secondary electrons produced by a high-energy Auger electron in water, and particularly to focus on the spatial and temporal distributions of the secondary electron and the collision events (e.g. ionization, electronic excitation, and dissociative electron attachment) that are involved in the multiplication of lesions at sites of DNA damage.

Enhancement of DNA double-strand break induction and cell killing by K-shell absorption of phosphorus in human cell lines.

Purpose: To investigate an enhancement of DNA double-strand break (DSB) induction and cell killing effect by K-shell ionization of phosphorus atoms and Auger electrons on human cell lines.

Materials And Methods: Induction of DSB, DNA damage responses, cell cycle distributions, and cell killing effects were investigated after exposures of the cells with monochromatic synchrotron radiation soft X-rays of 2153 and 2147 eV, which were the resonance peak and off peak, respectively, of the K-shell photoabsorption of phosphorus.

Results: Higher biological effects in the cells irradiated with soft X-rays at 2153 eV than at 2147 eV were observed in (i) the efficiency of 53BP1/γ-H2AX co-localized foci formation per dose and residual number of foci, (ii) prolonged phosphorylation levels of DSB repair and/or cell cycle checkpoint related proteins and G2 arrest, (iii) the cell killing effects at the 10% survival level of normal human fibroblasts, HeLa cells, and human glioblastoma M059K cells (1.

Evaluation of DNA damage induced by Auger electrons from Cs.

Purpose: To understand the biological effect of external and internal exposure from Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from Cs was compared with that induced by Cs γ-rays.

Methods: Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale.

Cellular automaton-based model for radiation-induced bystander effects.

Background: The radiation-induced bystander effect is a biological response observed in non-irradiated cells surrounding an irradiated cell. The bystander effect is known to be induced by two intercellular signaling pathways, the medium-mediated pathway (MDP) and the gap junctional pathway (GJP). To investigate the relative contribution of each signaling pathway, we have developed a mathematical model of the cellular response through these two pathways, with a particular focus on cell-cycle modification.

Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations.

The aim of this report is to present the spectrum of initial radiation-induced cellular DNA damage [with particular focus on non-double-strand break (DSB) damage] generated by computer simulations. The radiation types modeled in this study were monoenergetic electrons (100 eV-1.5 keV), ultrasoft X-ray photons Ck, AlK and TiK, as well as some selected ions including 3.

A mathematical model of radiation-induced responses in a cellular population including cell-to-cell communications.

Cell-to-cell communication is an important factor for understanding the mechanisms of radiation-induced responses such as bystander effects. In this study, a new mathematical model of intercellular signalling between individual cells in a cellular population is proposed. The authors considered two types of transmission of signals: via culture medium and via gap junction.

Radial dependence of lineal energy distribution of 290-MeV/u carbon and 500-MeV/u iron ion beams using a wall-less tissue-equivalent proportional counter.

Using a wall-less tissue-equivalent proportional counter for a 0.72-μm site in tissue, we measured the radial dependence of the lineal energy distribution, yf(y), of 290-MeV/u carbon ions and 500-MeV/u iron ion beams. The measured yf(y) distributions and the dose-mean of y, [Formula: see text], were compared with calculations performed with the track structure simulation code TRACION and the microdosimetric function of the Particle and Heavy Ion Transport code System (PHITS).

Visualisation of γH2AX foci caused by heavy ion particle traversal; distinction between core track versus non-track damage.

Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised.

Induction of DNA damage, including abasic sites, in plasmid DNA by carbon ion and X-ray irradiation.

DNA from plasmid pUC18 was irradiated with low-LET (13 keV/μm) or high-LET (60 keV/μm) carbon ions or X-rays (4 keV/μm) in solutions containing several concentrations of Tris (0.66-200 mM) to determine the yield of abasic (AP) sites and the effect of scavenging capacity. The yield of AP sites, detected as single-strand breaks (SSB) after digestion with E.

Development of a simulation method for dynamics of electrons ejected from DNA molecules irradiated with X-rays.

Purpose: To develop a method for simulating the dynamics of the photoelectrons and Auger electrons ejected from DNA molecules irradiated with pulsed monochromatic X-rays.

Materials And Methods: A 30-base-pair (bp) DNA molecule was used as the target model, and the X-rays were assumed to have a Gaussian-shaped time distribution. Photoionization and Auger decay were considered as the atomic processes.

Yield of single- and double-strand breaks and nucleobase lesions in fully hydrated plasmid DNA films irradiated with high-LET charged particles.

We measured the yield and spectrum of strand breaks and nucleobase lesions produced in fully hydrated plasmid DNA films to determine the linear energy transfer (LET) dependence of DNA damage induced by ion-beam irradiation in relation to the change in the atomic number of ions. The yield of isolated damage was revealed as a decrease in prompt SSBs with increasing LET of He(2+), C(5+,6+) and Ne(8+,10+) ions. On the other hand, the yields of prompt DSBs increased with increasing ion LET.

Applications of the microdosimetric function implemented in the macroscopic particle transport simulation code PHITS.

Purpose: Microdosimetric quantities such as lineal energy are generally considered to be better indices than linear energy transfer (LET) for expressing the relative biological effectiveness (RBE) of high charge and energy particles. To calculate their probability densities (PD) in macroscopic matter, it is necessary to integrate microdosimetric tools such as track-structure simulation codes with macroscopic particle transport simulation codes.

Methods: As an integration approach, the mathematical model for calculating the PD of microdosimetric quantities developed based on track-structure simulations was incorporated into the macroscopic particle transport simulation code PHITS (Particle and Heavy Ion Transport code System).

Monte Carlo simulation of radial distribution of DNA strand breaks along the C and Ne ion paths.

Radial energy deposition distribution, the distribution of DNA strand breaks and their yields were simulated by Monte Carlo track structure simulation for C and Ne ions with the same linear energy transfer (LET) around 450 keV/μm. The radial DNA damage distribution shows different pattern for C and Ne ions. Double strand break (DSB) are mostly formed in the central area, while the single strand break (SSB) tends to spread to the surrounding area.

Induction of DNA strand breaks, base lesions and clustered damage sites in hydrated plasmid DNA films by ultrasoft X rays around the phosphorus K edge.

To characterize the DNA damage induced by K-shell ionization of phosphorus atom in DNA backbone on the level of hydration, the yields of DNA strand breaks and base lesions arising from the interaction of ultrasoft X rays with energies around the phosphorus K edge were determined using dry and fully hydrated pUC18 plasmid DNA samples. Base lesions and bistranded clustered DNA damage sites were revealed by postirradiation treatment with the base excision repair proteins endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The yield of prompt single-strand breaks (SSBs) with dry DNA irradiated at the phosphorus K resonance energy (2153 eV) is about one-third that below the phosphorus K edge (2147 eV).

Estimation of yields of hydroxyl radicals in water under various energy heavy ions.

This article reports the determination of yields of OH (hydroxyl) radicals in water irradiated with helium, carbon, neon and argon ions ranging from 2 to 18 MeV/nucleon. The yields of the OH radicals depend on the atomic number and energy of the incident ion and the reaction time just after the irradiation based on the track structure theory. The yields of the OH radicals estimated by analyzing the yields of the irradiation products from phenol were at almost 0 to 3.