Early Radiation Damage Research Articles

Positron annihilation spectroscopy evaluation of using proton irradiation as a surrogate for early neutron radiation damage

A positron annihilation spectroscopy investigation of early stages of radiation-induced damage in Chinese f/m (ferritic/martensitic) steel SIMP and strengthened variant of f/m steel ODS (oxide dispersion strengthened) EUROFER was conducted. Studied materials were irradiated by neutrons at the LVR-15 research reactor to 0.12 dpa at an average temperature of 260 ± 20 °C, and implanted by protons at the 6 MV Tandetron Accelerator of the Slovak University of Technology, to 0.0196 dpa at room temperature (RT) and 300 °C. The potential of using proton irradiation as a surrogate for early neutron radiation damage was investigated. A lifetime spectrometer and Doppler spectrometer was used to obtain simultaneously positron lifetime (PALS) and Doppler broadening spectra (DBS), which provided experimental data used to characterize the vacancy-type defect and their interaction with H atoms in the studied materials. The obtained results show an increase of mean positron lifetime (MLT) in the proton-implanted samples at RT when compared with high temperature irradiation. Similar trend was observed when comparing vacancy concentration of different irradiation conditions. The impact of temperature on mobility and recombination of defects, as well as effect of vacancy stabilization by H atoms, has been addressed. The effect of ODS microstructure on results has been examined. A methodology of comparing various irradiation conditions has been proposed, where the vacancy concentrations have been normalized by the dpa values. The potential application of proton implantation for evaluation of early stages of neutron damage was found to be promising.

Early and late facial neuropathy after radiosurgery of vestibulocochlear schwannomas

Stereotactic radiosurgery (SRS) is the method of choice for the treatment of vestibular schwannomas, due to its high frequency of tumor growth control and low complication rate. According to the world scientific literature, one of the rare late radiation induced complications is facial nerve paralysis. It is extremely rare to find reports of cases of prosoparesis that occurred during the first week after performing SRS. The potential etiology, pathogenesis, and management of this type of complication still remain a subject for discussion. As potential risk factors for the development of radiation-induced complications for cranial nerves, such indicators as the patient's age, the maximum diameter of the tumor, the presence of a fundal fluid cap, the amount of prescribed, average and maximum radiation dose per cochlea, the extent of the tumor's contact with the nerve trunk, or the radiation dose beyond the boundaries of the tumor are currently being studied. However, further study of predictors of the post-radiation neuropathy requires cohort studies. The article presents two cases of early and late radiation-induced neuropathy of the facial nerve after radiosurgery of vestibular schwannomas. Predictors and risk factors for the development of this type of complications after SRS are discussed. The important role of steroid therapy in the complex treatment of this group of patients was noted. In the presented patients, no reliable pathogenetic mechanisms leading to early radiation damage to the facial nerve were revealed. Despite the restoration or improvement of the strength of facial muscles, complications of facial neuropathy (hypertension, synkinesia) developed, which required timely detection and correction with the mandatory supervision of a neurologist.

Orthovoltage X-Ray Therapy of Large Cell Invasive Nasal Lymphoma in Cat

Abstract Feline nasal lymphoma is generally a localized radiosensitive tumor. Treatment options include radiation therapy, chemotherapy, or a combination of both modalities. Radiation therapy (RT) in a combination with chemotherapy lead to median survival from 19 months to 955 days. The objective of this paper is to report a case of a large cell late stage invasive feline nasal lymphoma and to evaluate the results of orthovoltage radiation therapy and its side effects. A 12-year-old female mixed breed cat was presented with nasal discharge, sneezing and hyporexia. Definitive histopathology diagnosis was diffuse large cell lymphoma. Computed tomography revealed an advanced stage of the disease, an intranasal mass, bone lysis, invasion of the orbital space and central nervous system. A radical course of X-ray therapy was performed (SFD = 4 Gy, TSD = 40 Gy, 10 sessions, 3 times a week). Radiation side effects were well tolerated and resolved with supportive treatment. Lymphoma is a systemic process and requires a multidisciplinary approach. On most cases, the penetrating ability of radiation therapy of 3.5 cm in depth is enough for small domestic animals. A significant effect is noted in the middle of the treatment course. The fractionated regime did not cause early radiation damage. The relapse-free period was up to 8 months. The patient had a satisfying quality of life for 5 months. Orthovoltage X-ray therapy can be considered as a treatment choice for local nasal lymphoma. X-ray therapy is a widely used modality in veterinary medicine considering the price of machines and costs of treatment.

Cosmic Radiations and the Cardiovascular System: A Narrative Review.

In recent times, space flights receive continued interest. Humankind's next two goals are to return to the Moon and, a few years later, to land on the surface of Mars. Although technology will improve enough to enable long voyages, there are still some unresolved questions about the effects of the space environment on human health, including the effects of such long voyages on organs. Specifically, there is no information on the effects of radiation in space on the human cardiovascular system. To better understand the adaptation of the cardiovascular system to radiation exposure, the physical properties of radiation and the cellular and molecular mechanisms underlying tissue changes are essential. To this end, this article aims to provide an overview of the effects of radiation on the cardiovascular system by analyzing the physical properties of radiation and their relationship to cellular and molecular mechanisms and potential changes. Each type of radiation triggers different responses in the cardiovascular system. Radiation plays a relevant role in altering endothelial function and arterial wall stiffness by inducing vascular changes that accelerate atherosclerosis and affect endothelial adhesiveness. Clinical studies have shown that vascular changes due to radiation depend on the delayed manifestations of early radiation damage. To reduce the effects of radiation in space, some pharmacological treatments that seem to be able to counteract oxidative stress during flight are being used. At the same time, new shielding systems that can reduce or eliminate radiation exposure must be developed. Future studies should aim to replicate flights in the deep space environment to study in more detail the harmful effects of radiation on the whole cardiovascular system.

An investigation of early radiation damage in rainbow trout eye-lenses.

As part of the wider interest in the effects of ionizing radiation on non-human biota, this investigation was carried out to study early radiation damage to the eye-lenses of rainbow trout. Lenses were cultured and irradiated to doses of 1.1 Gy and 2.2 Gy with low-energy X-rays of 40 kV. Laser focal analysis was used to track changes in focal lengths across the lenses post-irradiation. Changes in focal length variability (FLV) were measured to determine whether this could give an indication of the early effects of radiation on lens health. No statistically significant differences in FLV between the control and irradiated lenses within 10 days post-irradiation were observed. FLV was found to be 0.09 ± 0.02 mm for 2.2 Gy lenses, 0.06 ± 0.01 mm for 1.1 Gy lenses, and 0.11 ± 0.02 mm for control lenses at the end of the observation period.

Self healing of radiation-induced damage in Fe–Au and Fe–Cu alloys: Combining positron annihilation spectroscopy with TEM and ab initio calculations

Self healing of early stage radiation damage by site selective solute segregation is a promising approach to extend the lifetime of nuclear reactor components. In the present study, the creation and autonomous healing of irradiation-induced damage is investigated in pure Fe and high purity Fe–Au and Fe–Cu model alloys. To create radiation damage samples are irradiated at 550 °C by 120 keV He+ ions with fluences of 5.0 × 1015, 1.0 × 1016 and 5.0 × 1016 ions/cm2. The observed increase in the S and W parameters determined in the variable energy positron annihilation spectroscopy measurements indicates the formation of vacancy-like defects, precipitates and vacancy-solute complexes. The presence of substitutionally dissolved Au is found to reduce the formation of radiation defects more efficiently than solute Cu. Site-specific Au precipitation at defect sites is indicated, which results in damage healing with a reduced swelling, whereas Cu precipitates and radiation damage only show weak interaction. Ab initio calculations show that the binding energies of Au solutes to vacancy clusters (Au-Vn) are significantly larger than those of Cu solutes (Cu-Vn) whereas the binding energies of helium filled vacancy clusters Au-HenVn and Cu-HenVn are comparable.

INVESTIGATION INTO THE PROBABILITY FOR MISCOUNTING IN FOCI-BASED ASSAYS.

When early radiation damage to biological systems is studied based on the formation of foci at the location of DNA double-strand breaks, the foci observed in irradiated cells either may be induced by ionizing radiation (IR) interactions or they may be due to other causes that lead to observation of foci also in unirradiated cells. Generally, to take account of the latter, additional samples are taken where the exposure to IR is skipped in the protocol. The data analysis relies on statistical independence of the frequency distributions of background and radiation-induced foci. In microscopy, however, the observed spatial patterns of foci are 2D projections of the spatial distributions of foci in the observed cell nuclei. This may lead to missing foci when scoring their number, particularly if projections of foci overlap or coincide. This paper investigates to what extent the statistical independence of the frequency distribution of the number of foci coming from IR interaction or other causes is compromised by foci overlapping.

Using Space-Time Correlations to Identify Transient Defects

ABSTRACTAtomistic simulations are employed to investigate the dynamical behavior of atoms in cubic silicon carbide (SiC) following a 5 keV radiation knock. Specifically, we have computed the time-resolved van Hove self-correlation function, Gs(r,t), separately for the silicon and carbon sub-lattices. Our goal is to probe the early radiation damage mechanisms using a dynamical methodology. The simulation results show that the carbon atoms engage in a dynamic hopping mechanism as the system recovers from the radiation knock. The silicon atoms, however, exhibit a strikingly different behaviour: the time variation of 4πr2Gs(r,t) indicates a dynamic tension between the crystalline and disordered regions of the Si sub-lattice. The power-law tail of the 4πr2Gs(r,t) correlation for silicon atoms suggests a scale-free self-organized critical (SOC) state – a possible precursor to the collapse of the Si sub-lattice.

Early Effects of Ionizing Radiation on the Collagen Hierarchical Structure of Bladder and Rectum Visualized by Atomic Force Microscopy.

Radiation therapy, widely used in the treatment of a variety of malignancies in the pelvic area, is associated with inevitable damage to the surrounding healthy tissues. We have applied atomic force microscopy (AFM) to track the early damaging effects of ionizing radiation on the collagen structures in the experimental animals' bladder and rectum. The first signs of the low-dose radiation (2 Gy) effect were detected by AFM as early as 1 week postirradiation. The observed changes were consistent with initial radiation destruction of the protein matrix. The alterations in the collagen fibers' packing 1 month postirradiation were indicative of the onset of fibrotic processes. The destructive effect of higher radiation doses was probed 1 day posttreatment. The severity of the radiation damage was proportional to the dose, from relatively minor changes in the collagen packing at 8 Gy to the growing collagen matrix destruction at higher doses and complete three-dimensional collagen network restructuring towards fibrotic-type architecture at the dose of 22 Gy. The AFM study appeared superior to the optical microscopy-based studies in its sensitivity to early radiation damage of tissues, providing valuable additional information on the onset and development of the collagen matrix destruction and remodeling.

Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA

In order to improve the understanding of the mechanisms involved in the generation of early DNA damage, a new calculation chain based on the Geant4-DNA toolkit was developed. This work presents for the first time the simulation of the physical, physicochemical and chemical stages of early radiation damage at the scale of an entire human genome (fibroblast, male) and using Geant4-DNA models. The DnaFabric software was extended to generate and export this nucleus model to a text file with a specific format that can be read by Geant4 user applications. This calculation chain was used to simulate the irradiation of the nucleus by primary protons of different energies (0,5; 0,7; 0,8; 1; 1,5; 2; 3; 4; 5; 10; 20 MeV) and the results, in terms of DNA double strand breaks, agree with experimental data found in the literature (pulsed field electrophoresis technique). These results show that the simulation is consistent and that its parameters are well balanced. Among the different parameters that can be adjusted, our results demonstrate that the criterion used to select direct strand break appears to have a very significant role on the final number of simulated double strand breaks.

Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage.

Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. Animal experimentation. Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT). Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and matrix metal-loproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. VA decreased the levels of TNF-α and IL-1β proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition.

Anti-Inflammatory and Anti-Apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage

Anti-Inflammatory and Anti-Apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage

OC-0052: Differences in dose-volume effects between early and late radiation damage in rat lung

OC-0052: Differences in dose-volume effects between early and late radiation damage in rat lung

Biologically Weighted Quantities in Radiotherapy: an EMRP Joint Research Project

Funded within the European Metrology Research Programme (EMRP) [1], the joint research project “Biologically weighted quantities in radiotherapy” (BioQuaRT) [2] aims to develop measurement and simulation techniques for determining the physical properties of ionising particle tracks on different length scales (about 2 nm to 10 μm), and to investigate the correlation of these track structure characteristics with the biological effects of radiation at the cellular level. Work package 1 develops micro-calorimeter prototypes for the direct measurement of lineal energy and will characterise their response for different ion beams by experiment and modelling. Work package 2 develops techniques to measure particle track structure on different length scales in the nanometre range as well as a measurement device integrating a silicon microdosimeter and a nanodosimeter. Work package 3 investigates the indirect effects of radiation based on probes for quantifying particular radical and reactive oxygen species (ROS). Work package 4 focuses on the biological aspects of radiation damage and will produce data on initial DNA damage and late effects for radiotherapy beams of different qualities. Work package 5 provides evaluated data sets of DNA cross-sections and develops a multi-scale model to address microscopic and nanometric track structure properties. The project consortium includes three linked researchers holding so-called Researcher Excellence Grants, who carry out ancillary investigations such as developing and benchmarking a new biophysical model for induction of early radiation damage and developing methods for the translation of quantities derived from particle track structure to clinical applications in ion beam therapy.

Early radiation-induced mucosal changes evaluated by proctoscopy: Predictive role of dosimetric parameters

Background and purposeLate rectal complications are assessed according to different scoring systems. Endoscopy can provide a more sensitive estimation of early radiation damage. The aim of this paper is to investigate the correlation between dosimetric parameters and rectal mucosal changes after radiotherapy (RT). Materials and methodsPatients with prostate adenocarcinoma treated with curative or adjuvant RT underwent endoscopy 1year after RT. Receiver operating characteristics (ROC) analysis was performed to analyze the predictive capability of the dosimetric variables in determining mucosal changes classified by Vienna Rectoscopy Score (VRS). ResultsThe best dosimetric predictors of grade ⩾2 telangiectasia were rectal (r) V60 Gy (p=0.014), rV70 Gy (p=0.017) and rDmean (p=0.018). Similar results were obtained for grade ⩾2 VRS. The set of rV60 Gy<34.4%, rV70 Gy<16.7% and rDmean<57.5Gy was associated with a decreased risk of grade ⩾2 telangiectasia and VRS. ConclusionsrV60 Gy, rV70 Gy and rDmean were the strongest predictors of rectal mucosal alterations. In-depth analysis is required to correlate each mucosal alteration with late rectal toxicity in order to suggest early proctoscopy as surrogate end-point for rectal late toxicity in studies aimed at reducing this important complication.

A Simple Quantitative Method for Assessing Pulmonary Damage after X Irradiation

Pulmonary damage after radiotherapy is typically characterized by an initial alveolar inflammation (pneumonitis) followed by chronic fibrosis. In the present study, changes in lung architecture were measured in the pneumonitis phase after whole-body low-dose X irradiation of C57BL/6 mice. Radiation damage was evaluated at 24 h and 1-8 weeks postirradiation. Three distinct scoring systems were used: ( 1 ) manually evaluating alveolar distortion and infiltration of inflammatory cells into the alveolar space using a continuous numerical scale across an entire lung section, ( 2 ) physically measuring the average thickness of the alveolar septa from multiple representative microscope fields, and ( 3 ) a new rapid automated mathematical algorithm based on image segmentation of alveolar space across an entire section. Each scoring method detected significant changes in alveolar architecture at the earliest times compared with sham-treated controls and gave comparable evaluations of injury. The results from the automated mathematical algorithm correlated significantly with both the manual evaluation method (Spearman's correlation coefficient rho = 0.044) and the direct physical measurement of septa thickness (rho = 0.002). These data demonstrate that evaluating alveolar space by segmentation analysis provides a reliable method for scoring early pulmonary radiation damage that is consistent with more established methodologies but is more rapid and is independent of potential operator and selection bias.

On the mechanism of salivary gland radiosensitivity

To contribute to the understanding of the enigmatic radiosensitivity of the salivary glands by analysis of appropriate literature, especially with respect to mechanisms of action of early radiation damage, and to supply information on the possibilities of amelioration of radiation damage to the salivary glands after radiotherapy of head-and-neck cancer. Selected published data on the mechanism of salivary gland radiosensitivity and radioprotection were studied and analyzed. From a classical point of view, the salivary glands should not respond as rapidly to radiation as they appear to do. Next to the suggestion of massive apoptosis, the leakage of granules and subsequent lysis of acinar cells was suggested to be responsible for the acute radiation-induced function loss of the salivary glands. The main problem with these hypotheses is that recently performed assays show no cell loss during the first days after irradiation, while saliva flow is dramatically diminished. The water secretion is selectively hampered during the first days after single-dose irradiation. Literature is discussed that shows that the compromised cells suffer selective radiation damage to the plasma membrane, disturbing signal transduction primarily affecting watery secretion. Although the cellular composition of the submandibular gland and the parotid gland are different, the damage response is very alike. The acute radiation-induced function loss in both salivary glands can be ameliorated by prophylactic treatment with specific receptor agonists. The most probable mechanism of action, explaining the enigmatic high radiosensitivity for early effects, is selective radiation damage to the plasma membrane of the secretory cells, disturbing muscarinic receptor stimulated watery secretion. Later damage is mainly due to classical mitotic cell death of progenitor cells, leading to a hampered replacement capacity of the gland for secretory cells, but is also caused by damage to the extracellular environment, preventing proper cell functioning.

Volume effects and region-dependent radiosensitivity of the parotid gland

To detect volume effects and possible regional differences in radiosensitivity of the rat parotid gland. Parotid glands of male albino Wistar rats were locally X-irradiated, with collimators with conformal radiation portals used to supply 100% volume and 50% cranial/caudal partial volumes. High-resolution magnetic resonance imaging was used to provide the outlines of the parotid glands. Single doses of up to 40 Gy were applied, and the effects on saliva secretion, measured with the aid of miniaturized Lashley cups, were followed up to 365 days after the irradiation. Under conditions of equal mean absorbed doses and small variations in dose distribution, a pertinent volume effect was observed for late but not for early radiation damage. The late effects were different for the cranial part as compared with the caudal part of the parotid gland. The reduction in flow rate was much more severe after irradiation in the cranial part. After a single dose of 30 Gy, the reductions in flow rates were approximately 65% and 25% for the cranial and caudal parts, respectively. At that dose, no saliva flow was observed after irradiation of 100% of the gland. From the rat model studies presented, it is concluded that late radiation damage after partial irradiation of parotid glands shows region-dependent volume effects. This finding is expected to be relevant to the radiosensitivity of human salivary glands, and it implies that the predictive power of the mean dose concept in radiotherapeutic practice is limited. The finding of region-dependent late radiation damage also challenges the basic assumptions of most current normal tissue complication probability models for parotid gland function.

Radiation-induced apoptosis: a new approach using infrared microspectroscopy

to characterize radiation-induced apoptosis in human cells using Fourier transform infrared microspectroscopy (FT-IRM) as a new analytical tool. Normal human circulating lymphocytes were given a gamma ray dose of 6 Gy, or treated with t-butyl hydroperoxide (t-BuOH). HaCaT keratinocytes were given a dose of 20 Gy. Cells were deposited on ZnS windows for infrared spectral acquisition 2 days and 2 h after irradiation and 2 h after t-BuOH treatment. Apoptosis was simultaneously assessed by flow cytometry analysis of cells displaying annexin-V-positive staining. The flow cytometry study showed that about 90% of sham and irradiated cells were annexin-V negative 2 h after irradiation. Two days after irradiation, 68% of lymphocytes and 76% of HaCaT cells were apoptotic, as well as 43% of lymphocytes treated with t-BuOH. In infrared spectra of these apoptotic cells, qualitative and quantitative changes were observed. In the 960-1245 and 1690-1720 cm-1 ranges, mainly attributed to nucleic acids, changes corresponding to conformational changes in DNA were associated with a decrease in the amount of detectable DNA. Conformational changes were also observed in secondary protein structure, in particular an increase in the amount of beta structures. These DNA and protein changes were associated with an increase in the detectable amount of lipids in apoptotic HaCaT cells only. Two hours after irradiation, depending on the dose and (or) the cell type, qualitative and quantitative changes were observed in the IR spectra in the amide I and amide II bands, mainly attributed to proteins. These changes were associated with a significant decrease in the 1700-1750 cm-1 range, mainly attributed to the -C=O ester groups of DNA and phospholipids, in the irradiated HaCaT cells only. Our results are in agreement with biochemical published data on radiation-induced apoptosis, and show that DNA is the first cellular target of radiation-induced apoptosis, which, however, also requires conformational changes and synthesis of cell proteins. They also demonstrate that FT-IRM may be useful for assessing the early radiation damage at the molecular level in human cells.

627 Poster Volume effects for early and late radiation damage in the parotid gland

627 Poster Volume effects for early and late radiation damage in the parotid gland