Chinese hamster V79-171B cells grown for about 24 hours in suspension culture display increased resistance to cell killing by ionizing radiation compared with cells grown as monolayers, an observation originally termed the "contact effect". More recently, development of that resistance was shown to be accompanied by changes in the conformation of the DNA which reduce its denaturation rate in high salt/weak alkali. These changes in DNA conformation, mediated by the cellular micro-environment, appear to be responsible for the contact effect. The conditions necessary for the development of the effect are not, however, completely understood. In particular, when cells grown as monolayers on petri plates are suspended in spinner culture flasks, their growth characteristics change in three distinct ways. First, cells in suspension no longer have a solid substrate, so they remain round. Second, after several hours, they begin to aggregate to form "spheroids", so that three-dimensional intercellular cell contact develops. Third, cells in the stirred suspension cultures are not subjected to high local concentrations of metabolic by-products or surrounded by a zone depleted of nutrients, as are cells in monolayer culture. The studies described here were designed to determine how each of these factors influence changes in DNA conformation, as assayed using the alkali unwinding technique. Our results indicated that a round shape may not be an essential requirement, since cells spread out on the surface of cytodex beads in suspension culture, and sparsely-seeded cells in monolayer culture demonstrated at least a partial contact effect. Three-dimensional intercellular contact does not always seem necessary for the development of the contact effect. Cells grown in a methyl cellulose matrix developed radioresistance, even though the cells formed only small clusters of less than five cells. Similarly, suspension culture cells which were prevented from aggregating by frequent exposure to trypsin, also developed the contact effect. There was no evidence that nutrient depletion plays a role in the failure of cells grown as monolayers to develop a contact effect. However, cells grown as spheroids in the presence of monolayer cells, or in monolayer cell-conditioned medium, did not display a full contact effect. This indicates a role for monolayer cell-produced factors (possibly extracellular matrix proteins) in preventing the development of the contact effect. We conclude that changes in DNA conformation and the increase in radiation resistance, seen in V79-171b cells grown as spheroids, are not the result of intercellular contact or round shape of the cells. This radioresistance appears to be the result of an absence of monolayer cell-produced factors which could control both cell shape and DNA conformation. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Thesis (MSc (Radiography))--Cape Peninsula University of Technology, 2019 / Introduction: Intracranial aneurysm coil embolization is a fluoroscopically guided interventional procedure that is often preferred over surgical clipping for the treatment of intracranial aneurysms. Fluoroscopically guided procedures are associated with high levels of radiation doses which have the potential to induce skin injuries; and this necessitates adherence to radiation protection measures, especially the optimization of radiation exposure during fluoroscopically guided procedures. Optimization of radiation exposure can be achieved by applying the as low as reasonably achievable (ALARA) principle and by implementing diagnostic reference levels (DRLs). Monitoring and documentation of radiation doses at the end of each procedure is also essential to identify patients that are at risk of developing radiation-induced injuries for possible follow-up. Aim: This research study aimed to determine the average radiation dose to patients' thyroid glands and skin during intracranial aneurysm coil embolization. The objectives were to establish preliminary DRLs for intracranial aneurysm coil embolization; to ascertain whether the anatomical location of the intracranial aneurysm had an effect on the radiation dose and to compare the measured thyroid gland and skin doses to the Monte Carlo calculated doses. Methods: A prospective quantitative research study was conducted on 34 participants who had intracranial aneurysms that required coil embolization during the study period. Radiation doses to the anterior neck of participants, over the thyroid gland region, were measured using lithium fluoride thermoluminescent dosimeters (TLDs). In addition, the air-kerma area product (KAP) values were used to determine the participants' skin dose and the DRLs. Considering that it is not possible to perform direct thyroid measurements on human beings, phantom-based simulation studies were performed to evaluate the difference between the dose measured on the anterior neck and the dose measured directly on the thyroid gland. Three different aneurysm coil embolization scenarios were simulated during the phantom-based simulation studies. TLDs were placed on the anterior neck and in the thyroid hole of the phantom, which represents the anatomical location of the thyroid gland, during each simulation. The thyroid and skin doses were also calculated using a Monte Carlo program. The measured thyroid gland and skin doses were compared to the doses obtained from Monte Carlo calculations. Results: The average percentage difference between the anterior neck doses and thyroid radiation doses was found to be 61%. This value was added to the radiation dose measured on the anterior neck of participants to obtain the thyroid absorbed doses during coil embolization procedures. The thyroid absorbed doses ranged between 3.2 and 20.95 mGy with a mean of 11.25 mGy. The KAP values ranged between 33 and 125 Gy.cm2. The DRL established during this study was 68 Gy.cm2, 616 image frames and 30 minutes of fluoroscopy time. There was no agreement between measured thyroid dose and calculated thyroid doses while there was strong positive correlation between measured and calculated skin doses. The results showed no statistically significant relationship between aneurysm location and the radiation dose. Conclusion: The skin doses in this research study were below the threshold doses suggested in the literature for deterministic effects of radiation. The study results therefore suggest that patients that undergo intracranial aneurysm coil embolization at the research site are not at risk of developing radiation-induced skin injuries. The established DRLs were also lower than internationally published DRLs for intracranial aneurysm coil embolization.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 1978. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Mohammad Seyed Saiedfar. / M.S.

In the course of experiments using uniaxial double alignment channeling to investigate radiation damage in single crystals, an anomalously large ion-scattering yield from the near surface of disordered or simulated disordered solid targets was observed. The chronology of the discovery of this new ion-solid effect and its explanation are presented along with experiments detailing the dependence of the new effect upon ion type and energy, as well as target atomic number and density. Targets included a spectrum of polycrystalline elemental targets in a range Z = 29 to Z = 82. Also, the influence of the effect upon scattering yields from an aligned Au(110) single crystal is demonstrated.

No description available.

The effects of low doses of ionizing radiation on living things is a continually evolving area of research. Importantly, low dose effects were historically overlooked and not properly accounted for the assessment of risk to human health, as is the case with the contentious linear no-threshold model. These low dose effects are now known to be relevant to human health in both accidental and intentional exposures, including doses relevant to medical diagnostics and therapeutics. Furthermore, there is a relative dearth of information on low dose effects in non-human species, which necessitates further investigation and evaluation of radiosensitivity. Radiation-induced bystander effects occur in organisms due to the receipt of signals from directly irradiated cells, which act to communicate radiation damage to surrounding cells. Recent research has identified one type of bystander signal which is carried by photons of biological origin, however the effects produced in bystander cells receiving these photons has not been extensively investigated. It was suspected, based on previous research, that reactive oxygen species participate in the manifestation of this bystander effect. Three mammalian cell lines were assessed for their ability to produce bystander photons upon direct irradiation; subsequently, radiologically unexposed cells were exposed to the resulting photons and assayed for biological effects. The human cell lines used exhibited significant photon emissions and oxidative stress, clonogenic cell death, reduced cellular metabolism, and compromised mitochondrial oxidative phosphorylation following exposure to these photons. The use of a melanocyte cell line indicated that these effects are attenuated by melanin, and this is suspected to occur through photoabsorption or antioxidant mechanisms. Additionally, the same assays were conducted following cell exposure to hydrogen peroxide at low concentrations to assess responses to oxidative stress relevant to bystander responses, indicating less overall sensitivity in the examined melanocytes. These findings are significant because they contribute to our understanding of the mechanisms behind low dose biological effects, because they further challenge the linear no-threshold model and other models based on target theory, because they provide evidence for differential responses to the physical bystander signal in non-human species, and because secondary photon emissions are likely relevant to the medical radiation sciences. / Thesis / Master of Science (MSc) / Low doses of ionizing radiation interact with living things differently than high doses. Low dose effects are now known to be relevant to human health and protection of the environment. Radiation-induced bystander effects occur in cells due to the receipt of signals from irradiated cells which act to communicate radiation damage to surrounding cells. One type of bystander signal is carried by photons emitted from directly irradiated cells, however the effects produced in bystander cells receiving these photons has not been extensively investigated. This thesis investigates the cellular effects of these “biophotons”, including cell survival, oxidative stress, and metabolism.

This thesis evaluates the suitability of silicon-germanium technology for electronic systems intended for extreme environments, such as ambient temperatures outside of military specification (-55 degC to 125 degC) range and intense exposures to ionizing radiation. Silicon-germanium devices and circuits were characterized at cryogenic and high-temperatures (up to 300 degC) and exposed to ionizing radiation, providing empirical evidence that silicon-germanium is an excellent platform for terrestrial and space-based electronic applications.

The mechanical behavior of structural materials used in nuclear applications is significantly degraded as a result of irradiation, typically characterized by an increase in yield stress, localization of inelastic deformation along narrow dislocation channels, and considerably reduced strains to failure. Further, creep rates are accelerated under irradiation. These changes in mechanical properties can be traced back to the irradiated microstructure which shows the formation of a large number of material defects, e.g., point defect clusters, dislocation loops, and complex dislocation networks. Interaction of dislocations with the irradiation-induced defects governs the mechanical behavior of irradiated metals. However, the mechanical properties are seldom systematically correlated to the underlying irradiated microstructure. Further, the current state of modeling of deformation behavior is mostly phenomenological and typically does not incorporate the effects of microstructure or defect densities. The present research develops a continuum constitutive crystal plasticity framework to model the mechanical behavior and deformed microstructure of bcc ferritic/martensitic steels exposed to irradiation. Physically-based constitutive models for various plasticity-induced dislocation migration processes such as climb and cross-slip are developed. We have also developed models for the interaction of dislocations with the irradiation-induced defects. A rate theory based approach is used to model the evolution of point defects generated due to irradiation, and coupled to the mechanical behavior. A void nucleation and growth based damage framework is also developed to model failure initiation in these irradiated materials. The framework is used to simulate the following major features of inelastic deformation in bcc ferritic/martensitic steels: irradiation hardening, flow localization due to dislocation channel formation, failure initiation at the interfaces of these dislocation channels and grain boundaries, irradiation creep deformation, and temperature-dependent non-Schmid yield behavior. Model results are compared to available experimental data. This framework represents the state-of-the-art in constitutive modeling of the deformation behavior of irradiated materials.

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: This study’s focus is on the determination and quantization of radiation damage on a cellular level due to the decay of the Auger electron-emitting 123I and the replication of this energy deposition using Geant4 Monte Carlo simulations. The relatively short half-life of 123I (13.2 hours) makes it ideal for studies of Auger electrons which induce biological damage similar to that of high linear energy transfer radiations, when permitted to deposit their energy in close proximity to DNA. Due to small cellular dimensions, direct dose measurements are impossible but estimates may be made from Monte Carlo simulations. In this investigation the thymidine analogue 5-[123I]-iodo-2-deoxyuridine (123IUdR) was used to incorporate the 123I into the cellular DNA of T-lymphocytes from two human donors. Radiation induced micronuclei were numerated in binucleated cells using fluorescence microscopy. The energy deposition per decay of 123I was calculated within a spherical geometry, having the same size and density as a human lymphocyte, using the open source Geant4 toolkit. The absorbed energy per disintegration was used to convert the incorporated 123I activity (Bq) into absorbed dose (Gy) values, in order to compare the biological damage caused by the radioactive iodine to 60Co γ-radiation. A linear relationship between micronuclei frequency and 123I activity could be established. The linear dose-response noted for Auger electrons in the study is indicative of the high-LET nature of these particles. Using the linear-quadratic dose-response curve for micronuclei frequencies following exposure to graded doses of 60Co γ-rays, the relative biological effectiveness (RBE) of the DNA incorporated 123I estimated in this work was found to range from 19 ± 10 to 32 ± 7 for lymphocyte donor 1 and 15 ± 6 to 42 ± 11 for donor 2. The dose limiting RBE (RBEM) for lymphocyte donor 1 and 2 are respectively 34 ± 8 and 50 ± 15 and follows the expected shift in terms of the inherent radiosensitivity of the donors. We also considered the inclusion of the S-phase fraction of the lymphocytes in the dosimetry calculations. The resultant RBEs of the dose points of lymphocyte donor 1 ranges from 4 ± 2 to 7 ± 2, and those of donor 2 ranges from 3 ± 1 to 9 ± 2. The RBEM for lymphocyte donor 1 and 2 are respectively 7 ± 2 and 11 ± 3. The inclusion of the S-phase fraction reduces the calculated RBEs significantly and these observed RBE values relate well to those obtained in studies with fibroblasts and 125IUdR. / AFRIKAANSE OPSOMMING: Hierdie studie fokus op die bepaling en kwantisering van stralingskade op 'n sellulêre vlak as gevolg van die verval van 123I wat Auger elektrone afgee, asook die simulering van hierdie energie afsetting met behulp van die Geant4 Monte Carlo program. Die relatiewe kort half-leeftyd van 123I (13.2 uur) maak dit ideaal vir studies van Auger elektrone wat biologiese skade soortgelyk aan dié van 'n hoë lineêre-energie-oordrag uitstraling veroorsaak, indien die energie van die elektrone naby sellulêre DNA geabsorbeer word. As gevolg van die klein sellulêre dimensies is direkte dosis metings egter onmoontlik, maar skattings kan gemaak word met behulp van Monte Carlo simulasies. Die timidien analoog 5-[123I]-jodo-2-deoxyuridien (123IUdR) was in hierdie ondersoek gebruik om die 123I in die DNA van menslike T-limfosiete in te bou. Mikrokerne in dubbel-kernige selle wat vorm as gevolg van die Auger elektrone was getel met behulp van fluoressensie mikroskopie. Die energie afsetting per 123I verval was bereken binne ‘n sferiese geometrie, met dieselfde grootte en digtheid as 'n menslike limfosiet, met behulp van die Geant4 sagteware. Die geabsorbeerde energie per verval was gebruik om die geïnkorporeerde 123I aktiwiteit (Bq) om te skakel na ‘n waarde van geabsorbeerde dosis (Gy), ten einde die biologiese skade wat veroorsaak word deur die radioaktiewe jodium-123 met kobalt-60 gamma straling te vergelyk. ‘n Lineêre verwantskap tussen die mikrokerne frekwensies en die 123I aktiwiteit is vasgestel. Hierdie verwantskap vir Auger elektrone is 'n aanduiding van die hoë lineêre-energie-oordrag van hierdie deeltjies. Die lineêr-kwadratiese dosis-effek krommes vir mikrokerne frekwensies na blootstelling aan 60Co γ-strale was gebruik om die relatiewe biologiese doeltreffendheid (RBE) van die DNA geïnkorporeerde 123I te beraam. RBE waardes wissel van 19 ± 10 tot 32 ± 7 vir limfosiete van skenker 1 en 15 ± 6 tot 42 ± 11 vir skenker 2. Die dosis beperkte RBE (RBEM) vir limfosiet skenker 1 en 2 is onderskeidelik 34 ± 8 en 50 ± 15 en volg die verwagte skuif in terme van die inherente radiogevoeligheid van die skenkers. Die fraksie van limfosiete wat in S-fase was tydens die blootstelling aan 125IUdR was ingesluit in verdere dosimetrie berekeninge. Die gevolglike RBEs van die dosispunte van limfosiete van skenker 1 wissel van 4 ± 2 tot 7 ± 2 en dié van skenker 2 wissel van 3 ± 1 tot 9 ± 2. Die RBEM vir limfosiet skenker 1 en 2 is onderskeidelik 7 ± 2 en 11 ± 3. Die insluiting van die S-fase fraksie verminder die berekende RBEs aansienlik en die RBE waardes waargeneem hou goed verband met die wat in studies met fibroblaste en 125IUdR verkry is.

In order to complete their life cycles, vertebrates require oxygen and water. However, environments are not always forgiving when it comes to constantly providing these basic needs for vertebrate life. The annual killifish Austrofundulus limnaeus is possibly the most well described extremophile vertebrate and its embryos have been shown to tolerate extremes in oxygen, salinity, and water availability. This phenotype is likely a result of the annual killifish life history, which includes periods of temporary habitat desiccation and oxygen deprivation, and requires the production of stress-tolerant embryos that depress metabolism in a state of suspended animation, known as diapause. Over the past several decades, the basic morphology and physiology of annual killifish development has become better characterized. However, there are still basic cellular processes that remain to be described in annual killifish such as A. limnaeus. Specifically, changes in DNA structure, expression, and copy number are known to have profound impacts on the phenotype and survival of an organism. Little is known as to how A. limnaeus maintains genome integrity during cell stress, nor how the A. limnaeus nuclear and mitochondrial genomes may have evolved under the unpredictable conditions in which A. limnaeus thrive. Early annual killifish embryonic development is also characterized by a complete dispersion and subsequent reaggregation of embryonic blastomeres prior to formation of the embryonic axis. This unusual period of early development may provide a functional adaptation that allows annual killifish embryos to survive these extreme conditions. The overall goals of this project were to (1) characterize the ability of A. limnaeus to tolerate and repair DNA damage through enzymatic and developmental mechanisms, (2) to determine possible consequences of mitochondrial DNA sequence and copy number on the metabolism of A. limnaeus, and (3) to establish a draft genome of A. limnaeus for future comparative genome studies. The results of this project show that embryos of A. limnaeus have an impressive ability to survive and reverse high doses of DNA damage induced by ultraviolet-C (UV-C) radiation, especially when allowed to recover under photoreactivating light. Surprisingly, embryos that survived irradiation during blastomere dispersion phases were able to develop normally. Characterization of gene expression during embryonic development for genes important for axis formation and cellular differentiation suggests that A. limnaeus embryos may delay axis formation until several days after epiboly is complete, thus allowing time for cells that become damaged to be replaced by surrounding pluripotent cells. This outcome would represent first case of a developmental buffering stage in a vertebrate. A. limnaeus embryos are also unique in their mitochondrial response to anoxia. Whereas in other species the amount of mitochondrial DNA (mtDNA) copy number fluctuates following extremes in oxygen availability, A. limnaeus embryonic mtDNA remains stable. Additionally, characterization of the fully sequenced A. limnaeus mitochondrial genome reveals possible evolutionary adaptations that may have facilitated dormancy and anoxia tolerance when compared to other species within the Order Cyprinodontiformes. The final chapter of this project characterizes the draft genome of A. limnaeus and I provide evidence suggesting that epigenetic DNA methylation that may be involved in regulating diapause.