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Colliaux, Anthony. "Implication de l’oxygène et des anti-oxydants dans le processus de radiolyse de l’eau induit par l’irradiation aux ions de haute énergie : simulations numériques pour la radiobiologie." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10297.
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Il s’agit d’étudier les effets du TEL du rayonnement, d’un soluté (oxygène, antioxydant, scavengers...) et d’une géométrie de confinement sur les processus physiques et chimiques. Nos études sur la production de radicaux libres en fonction de la pression d’oxygène et du TEL du rayonnement nous ont permis de noter une similitude entre la production des radicaux O2- / HO2 et l’effet oxygène décrit en radiothérapie. Ces résultats confortent l’idée que ce couple de radicaux pourraient jouer un rôle dans l’effet oxygène (radiothérapie) et expliqueraient la disparition de cet effet à haut TEL (hadronthérapie). Nous avons aussi montré que cette similitude persistait en présence de Glutathion (antioxydant majoritaire dans le noyau cellulaire)-
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Nasilowska, Agata. "The role of the CtIP gene as a genetic susceptibility factor for radiation leukaemogenesis." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:b8cc6940-e780-4ebd-8bf5-a655a52570d2.
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Exposure to ionising radiation increases the risk of cancer, including acute myeloid leukemia (AML), which is the most common myeloid leukaemia. The C-terminal binding protein (CtBP)-interacting protein (CtIP), which is essential for embryonic development and possibly functions as a tumour suppressor, has been identified as a strong candidate for susceptibility to radiation-induced AML (rAML).
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Massager, Nicolas. "Influence de la distribution de dose d'irradiation dans la variation de l'effet radiobiologique du traitement radiochirurgical par Gamma Knife." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210380.
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La radiochirurgie par Gamma Knife constitue une modalité thérapeutique reconnue de certaines affections cérébrales. Le traitement se base sur l’administration d’un rayonnement focalisé au niveau d’une cible intracrânienne. L’efficacité de ce traitement repose sur la délivrance d’une dose d’irradiation efficace au sein d’un volume-cible associé à la délivrance d’une dose d’irradiation négligeable à l’extérieur de ce même volume-cible. En pratique, la dose d’irradiation administrée à l’intérieur du volume-cible n’est pas distribuée de manière homogène, et la dose d’irradiation reçue par les tissus situés en-dehors du volume-cible n’est pas nécessairement faible. Notre travail est basé sur l’hypothèse que l’imperfection de la distribution de la dose d’irradiation au sein du volume-cible et en-dehors de celui-ci peut être responsable des échecs et des complications rencontrées en radiochirurgie. Dans deux modèles cliniques de traitement radiochirurgical, le schwannome vestibulaire et la névralgie du trijumeau, nous avons montré qu’il existait une relation entre les paramètres de distribution de dose d’irradiation et certains résultats du traitement radiochirurgical par Gamma Knife de ces pathologies. Nous avons développé deux modèles expérimentaux d’irradiation radiochirurgicale de rats, l’un ciblé sur le striatum et l’autre sur le nerf trijumeau, permettant d’analyser les conséquences histologiques des variations de la distribution de dose à l’intérieur du volume-cible ainsi qu’à distance de celui-ci. Nous avons démontré que la réponse radiobiologique des tissus irradiés était fortement dépendante de ce paramètre dosimétrique, et que ce dernier constituait une donnée de la planification chirurgicale aussi importante que la dose de prescription. Nous avons corrélé ces résultats avec certaines observations réalisées dans d’autres indications de traitement radiochirurgical ainsi que dans l’analyse histologique de tumeurs traitées par Gamma Knife. Ces études mettent en évidence le rôle important joué par l’optimalisation de la distribution de la dose d’irradiation dans l’amélioration des résultats cliniques du traitement radiochirurgical. Les valeurs optimales de la distribution de dose dans les différentes indications de traitement radiochirurgical doivent être recherchées, et les différentes méthodes mises à notre disposition lors de la planification dosimétrique pour améliorer la distribution de dose doivent être utilisées avec discernement pour obtenir la dosimétrie radiochirurgicale la plus parfaite possible.Doctorat en sciences médicales
info:eu-repo/semantics/nonPublished
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Kakolee, Kaniz Fatema. "Laser driven acceleration of ions and its application in radiobiology." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579733.
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Kiger, Jingli Liu. "Radiobiology of normal rat lung in Boron Neutron Capture Therapy." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/41286.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2006.Includes bibliographical references.
Boron Neutron Capture Therapy (BNCT) is a binary cancer radiation therapy that utilizes biochemical tumor cell targeting and provides a mixed field of high and low Linear Energy Transfer (LET) radiation with differing biological effectiveness. This project investigated the radiobiology of normal rat lung in BNCT and measured the relative biological effectiveness factors for the lung. Rat thorax irradiations were carried out with x-rays and neutrons with or without the boron compound boronophenylalanine-fructose (BPA-F). Monte Carlo radiation transport simulations were used to design the rat lung neutron irradiations. Among the neutron beam facilities available for BNCT at the MIT Research Reactor, the thermal neutron beam facility was found to provide a suitable dose distribution for this project. A delimiter was designed and constructed for the rat lung irradiations as a lithiated-polyethylene plate of 1.5 cm thickness with an aperture tapered from 4 to 3 cm in width to expose the lung to the beam and shield adjacent radiosensitive organs. The simulation design was validated with in-phantom measurements using gold foil activation and the dual ion chamber technique. By using a two-field irradiation, a relatively uniform dose distribution could be delivered to the rat lung. The mean lung dose rate was 18.7 cGy/min for neutron beam only irradiation and 37.5 cGy/min with neutrons plus BPA and a blood boron concentration of 18 gg/g.
(cont.) The delimiter designed for rat lung irradiation, and another similar delimiter, along with the animal holding box, all designed in this project, also serve as the apparatus for other small animal irradiations and cell irradiations at the thermal neutron facility at the MIT Research Reactor. An open-flow whole-body plethysmography system with fully automated signal processing programs was developed to non-invasively measure rat breathing rates and lung functional damage after lung irradiation. Noise reduction was carried out against high frequencies beyond the range of rat breathing frequency and large amplitude spikes due to abnormal animal movement. The denoised breathing signals were analyzed using the Fast Fourier Transform with a circular moving block in combination with the bootstrap for noise suppression and to allow estimation of the statistical uncertainty (standard deviation) of frequency measurements. The major frequency of the mean frequency spectrum was determined as the breathing frequency. The mean control breathing rate was 176 ± 13 (7.4%) min' (mean ± SD), and breathing rates 20% (- 3 SD) above the control average were considered to be abnormally elevated. The mean standard deviation of all measurements (n = 4269) was 2.4%. The dose responses of different irradiation groups with breathing rate elevation as the biological endpoint were evaluated with probit analysis. Two response phases of breathing rate elevation were observed as the early response phase (<100 days) and the late response phase (>100 days). The ED50 values for x-rays, neutrons only, and neutrons plus BPA during the early response phase, and neutrons plus BPA during the late response phase, were 11.5 ± 0.4 Gy, 9.2 + 0.5 Gy, 8.7 ± 0.6 Gy and 6.7 ± 0.4 Gy, respectively.
(cont.) The radiobiological weighting factors for the neutron beam (neutrons and photons), thermal neutrons only, %°B dose component during the early response phase, and 10B dose component during the late response phase were 1.24 ± 0.08, 2.2 ± 0.4, 1.4 ± 0.2, and 2.3 + 0.3, respectively. The histological damage to the lung during the late phase was also quantified with a histological scoring system. A set of linear dose response curves with histological damage as the endpoint was constructed. The radiobiological weighting factors for the different dose components were also determined at a degree of lung histological damage corresponding to a median histological score between the baseline (similar to the control) and the maximum. The weighting factors measured, 1.22 ± 0.09 for the thermal neutron beam and 1.9 + 0.2 for the o1B dose component, are consistent with the corresponding weighting factors measured using functional damage. The knowledge gained in these radiobiological studies of the normal rat lung indicates that the lung complications experienced by two patients in the Harvard-MIT clinical trial of BNCT for brain tumors do not appear to be related to the BNCT irradiations. This project is also helpful for evaluating the feasibility of BNCT for lung cancer.
by Jingli Liu Kiger.
Ph.D.
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Hanton, Fiona. "Laser ion acceleration from ultrathin foils and application to radiobiology." Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706690.
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Laser driven ion sources offer a potential alternative to conventional ion accelerators currently used in hadrontherapy for cancer treatment. The unique characteristics of the ion beams sets the basis for development toward therapeutic use. The work presented in this thesis seeks to overcome the present limitations of laser-driven ion accelerators and to demonstrate the ion beam parameters required to make this a viable treatment option. Ultra-thin copper and gold foil targets were irradiated with intense laser pulses at normal incidence by varying laser and target parameters. For copper, the peak ion energies were observed to quadratically scale with the dimensionless fluence parameter, suggesting efficient Radiation Pressure Acceleration in the Light Sail phase in a hybrid acceleration regime. For gold targets, the production of high peak ion energies of ~20 MeV, ~12 MeV/nucleon and 7.5 MeV/nucleon for H+, C6+ and Au45+ were observed, respectively. In particular, the Au45+ ion energies translate to approximately 1.5-2 GeV per Au ion (for energies exceeding and including the spectral peak). 2D PIC simulations were performed and were found to be in agreement with experimentally observed data. The radiobiological work focused on studying DNA Double Strand Breaks (DSBs) following the irradiation of AG01522 cells with proton and carbon ions at ultra-high dose rates of ≥10A˄9 Gys˄-1. This was done by quantitatively measuring the dispersion of 53BP1 foci over a 24 hour period for cells irradiated with 10 MeV (5 keV/μm) protons and 5 MeV/nucleon (310 keV/μm) carbon ions. The slow repair kinetics and large number of foci remaining at 24 hours from carbon ion irradiation was indicative of more severe DSBs compared to the lower LET exposure from protons. The relative biological effectiveness for protons and carbon ions were found to be RBE_1H = 1.6 ± 0.2 and RBE_12C = 13 ± 9.
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Renegar, Jackson Reid. "On the implementations of experimental methods using fluorescence microscopy in modern radiobiology." Thesis, Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37228.
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This thesis is intended as an introductory lab manual on the experimental methods using fluorescence microscopy in modern radiobiology research. It is written for those who are unfamiliar with biology research. It first covers the proper use of laboratory equipment and growth of cell cultures in the lab. Subsequent chapters provide overviews of relevant modern experimental techniques for the quantification of radiation induced DNA damage in cells, and detailed protocols for performing these procedures. Techniques covered include immunostaining with fluorescent antibodies, the comet assay, and plasmid DNA transfections. Results of some straightforward experiments using these techniques are presented.
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Almeida, Solange Maria de 1959. "Efeito da radiação de eletrons na reparação tecidual." [s.n.], 1996. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288893.
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Orientador: Frab Norberto BoscoloTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-07-22T03:00:44Z (GMT). No. of bitstreams: 1 Almeida_SolangeMariade_D.pdf: 5623908 bytes, checksum: b26c68566d3a5cc890cf18e225a7c0c1 (MD5) Previous issue date: 1997
Resumo: O presente trabalho teve como finalidade estudar o efeito de baixas doses de radiação de elétrons no processo de reparação tecidual em ratos. Para tanto, os animais sofreram um procedimento cirúrgico, onde foi produzida uma ferida retangular, medindo 2,3 cm por 1,4 cm, na sua região dorsal anterior. No momento da irradiação, as feridas produzidas foram protegidas, sendo irradiada somente uma região corresponde a 1,0 cm lateralmente à cada borda da ferida, com todo o restante do corpo do animal também protegido. A irradiação foi realizada para um grupo de animais, imediatamente após a abertura da ferida. O outro grupo sofreu a irradiação 3 dias após esse procedimento. O processo de reparação tecidual foi estudado aos 2, 4, 7, 11, 14, 17 e 21 dias após o procedimento cirúrgico para o primeiro grupo, enquanto para o segundo grupo de animais, a reparação tecidual foi avaliada 5, 7, 10, 14, 17, 20 e 24 dias também após a abertura da ferida. Cada grupo irradiado foi comparado com. grupos controles correspondentes, os quais não sofreram irradiação. O processo de reparação tecidual foi avaliado pelos seguintes métodos: coloração pela hematoxilina - eosina, que possibilitou avaliar a mortologia do tecido de granulação; reação histoquímica de metacromasia pelo azul de toluidina pH 4, podendo assim ser avaliada a síntese de glicosaminoglicanas e por fim, impregnação argêntica, onde foi observada a síntese de colágeno, através da microscopia de polarização (birrefringência). Os resultados obtidos mostraram que 1,0 Gy de radiação de elétrons com um feixe de 6 MéV, usou um retardo no processo de reparação tecidual, quando aplicado imediatamente e 3 dias após a abertura da ferida, sendo que quando comparados os dois grupos irradiados, para os dias 7, 14 e 17 , o efeito na reparação tecidual foi mais acentuado no grupo que sofreu irradiação 3 dias após a abertura da ferida
Abstract: The present search had the purpose to study the low dose electron irrradiation effect in the process of tissue repair in rats. In such a way, the animais were submitted to a surgical procedure, in which a rectangular wound was performed, measuring 2.3cm X 1.4cm on the fore dorsal area. At the moment of irradiation, the wounds were protected so that only an area near 1.0cm laterally to each b9rder of the wound was i rrad iated , being protected ali the rest ofthe animal body. The irradiation was performed in one group of animais immediately after the wounding procedure. The other group was irradiated three days after wounding. The process of tissue repair was studied at 2, 4, 7, 11, 14, 17 and 21 days after the surgical procedure on the first group, while for the other group of animais, tissue repair was evaluated at 5, 7, 10, 14, 17, 20 and 24 days, also after wounding. Each irradiated group was compared to corresponding control groups, which did not were submited irradiation. The tissue repair process was evaluated by the following methods: staining by haematoxylin-eosin in order to evaluating granulation tissue morphology; histochemical reaction of metachromasia by toluidin pH 4.0, so that it was possible to evaluate the synthesis of glucosaminglucans and at last, the silver impregnation, in which it was studied the collagen synthesis bymeans of polarizing microscopy. The results obtained showed that 1.0 Gy of electron irradiation with a 6 MeV beam caused a delay in the process of tissue repair, when applied immediately after and at three days after wounding. The comparison of both irradiated groups at days 7, 14 and 17, have showed that the effect on tissue repair was stronger on the group that received irradiation 3 days after wounding
Doutorado
Radiologia
Doutor em Odontologia
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Bloch, Jonatas Carrero. "Avaliação de técnicas radioterápicas conformacionais utilizando critérios físicos e biológicos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/59/59135/tde-26062012-160955/.
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No combate às neoplasias, diferentes técnicas radioterápicas têm surgido, apoiadas em avanços tecnológicos, com o objetivo de otimizar a eliminação das células tumorais produzindo o menor dano a tecidos sadios dos pacientes. Os planejamentos de tratamentos radioterápicos visam o estabelecimento de parâmetros técnicos de irradiação de forma que as doses prescritas nos volumes de tratamento sejam atingidas. Enquanto que a prescrição das doses se baseiam em considerações biológicas de radiosensibilidade dos tecidos, os cálculos físicos do planejamento levam em conta parâmetros dosimétricos associados aos feixes de radiação e às características físicas dos tecidos irradiados. A incorporação de informações de sensibilidade de tecidos aos cálculos radioterápicos pode auxiliar na particularização de tratamentos e no estabelecimento de critérios de comparação e escolha de técnicas radioterápicas, contribuindo para o controle tumoral e sucesso do tratamento. Para tanto, modelos biológicos de resposta celular à radiação ionizante devem ser bem estabelecidos. Este trabalho visou estudar a aplicabilidade do uso de modelos biológicos em cálculos de planejamento radioterápico com objetivo de auxiliar na avaliação de técnicas radioterápicas. A probabilidade de controle tumoral (TCP) foi estudada para duas formulações do modelo linear-quadrático, com e sem consideração de repopulação celular, em função de parâmetros de planejamento, como dose por fração, e de parâmetros radiobiológicos, como a razão ?/?. Além disso, o uso de critérios biológicos para comparação de técnicas radioterápicas foi testado através da simulação de um planejamento de próstata utilizando simulação Monte Carlo com o código PENELOPE. Posteriormente, planejamentos radioterápicos de tumores de próstata de cinco pacientes do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, USP, utilizando-se três técnicas de irradiação diferentes, foram comparados através do critério de probabilidade de controle tumoral. Para tanto, matrizes de dose obtidas do sistema de planejamento radioterápico XiO foram utilizadas para obter as distribuições de TCP e histogramas TCP-volume. Os estudos realizados permitiram concluir que variações em parâmetros radiobiológicos podem influenciar significativamente cálculos de controle tumoral e que a análise de histogramas TCP-volume pode fornecer informações importantes para avaliação de tratamentos radioterápicos. Entretanto, o estabelecimento de fatores quantitativos de comparação através de critérios radiobiológicos passa pelo estabelecimento de protocolos de prescrição clínica baseados nesses critérios. Além disto, valores radiobiológicos sofreram grandes alterações na literatura recentemente e, portanto, a inclusão destes parâmetros nos cálculos de planejamentos requer grandes cuidados.In the fight against cancer, different irradiation techniques have been developed based on technological advances and aiming to optimize the elimination of tumor cells with the lowest damage to healthy tissues. The radiotherapy planning goal is to establish irradiation technical parameters in order to achieve the prescribed dose distribution over the treatment volumes. While dose prescription is based on radiosensitivity of the irradiated tissues, the physical calculations on treatment planning take into account dosimetric parameters related to the radiation beam and the physical characteristics of the irradiated tissues. To incorporate tissue\'s radiosensitivity into radiotherapy planning calculations can help particularize treatments and establish criteria to compare and elect radiation techniques, contributing to the tumor control and the success of the treatment. Accordingly, biological models of cellular response to radiation have to be well established. This work aimed to study the applicability of using biological models in radiotherapy planning calculations to aid evaluating radiotherapy techniques. Tumor control probability (TCP) was studied for two formulations of the linear-quadratic model, with and without repopulation, as a function of planning parameters, as dose per fraction, and of radiobiological parameters, as the ?/? ratio. Besides, the usage of biological criteria to compare radiotherapy techniques was tested using a prostate planning simulated with Monte Carlo code PENELOPE. Afterwards, prostate plannings for five patients from the Hospital das Clínicas da Faculdadede Medicina de Ribeirão Preto, USP, using three different techniques were compared using the tumor control probability. In that order, dose matrices from the XiO treatment planning system were converted to TCP distributions and TCP-volume histograms. The studies performed allow the conclusions that radiobiological parameters can significantly influence tumor control calculations and that the TCP-volume histograms can provide important information for treatment techniques evaluation. However, the establishment of quantitative comparison parameters using radiobiological criteria demands the establishment of prescription protocols based on these same parameters. Also, the literature recently showed large variations in radiobiological parameters, meaning that the inclusion of those in treatment planning calculations should require a careful endeavor.
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Prade, H. "Workshop on X-rays from electron beams." Forschungszentrum Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:d120-qucosa-30011.
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Prade, H. "Workshop on X-rays from electron beams." Forschungszentrum Rossendorf, 2000. https://hzdr.qucosa.de/id/qucosa%3A21828.
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Wang, Hsiao-Hsien. "Cytotoxic effects of a novel nitric oxide donor compound and oncogenic transformation of a human urothelial cell line." Thesis, University of St Andrews, 1995. http://hdl.handle.net/10023/14088.
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Transitional cell carcinoma of the bladder is commonly encountered in urological practice. It affects people of a relatively young age causing economic and social distress to patients. In order to prevent the disease it is important to understand its pathogenesis. In this study, we have tumorigenically transformed a human urothelial cell by growing cells in a serum free, factor free, chemically defined culture. The tumorigenic property of the cell was determined by the generation of a tumor after inoculation into nude mouse. DNA fingerprinting analysis demonstrated the common back ground of the non-tumorigenic human urothelial cell and its tumorigenic transformant. This result also shows evidence of mutation occurring during transformation. By analysing conditioned medium, a significant reduction in the levels of soluble human stem cell factor and interleukin la were found in tumorigenic cell conditioned medium. A model derived from this evidence may suggest that tumor cells undergo further transformation under nutrient and growth factor deprived conditions. Intravesical chemotherapeutic agents in current use have shown moderate tumor-killing effects with some systemic or local side effects. Identification of a drug with better effect and less side effects is essential for the successful treatment of bladder tumors. Nitric oxide (NO) is a natural product of the human body with a role in tumor cell-killing. Thus by using NO as a chemotherapeutic agent we could at least expect limited side effects. Roussin's black salt (RBS) is a novel NO donor. Its cytotoxicity was tested on tumorigenic (T24) and non-tumorigenic (SV-HUC-1) human urothelial cells. The cytotoxicity of RBS was shown to be dose- and contact time- dependent. This cytotoxicity was enhanced by light irradiation and reduced in the presence of haemoglobin. The cytotoxic effect of RBS was also tested on CHO cells and the DNA repair deficient mutant xrs-5 cell line. Both colony forming and micronuclei forming assays demonstrated that xrs-5 cells are more sensitive to RBS than their counterpart. This result may indicate that NO is involved in the cytotoxicity of RBS and furthermore that DNA damage might be one possible mechanism by which the cytotoxic effect of RBS is expressed.
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Lehane, Margaret. "Radiation quality as a determinant of transformed cell phenotypes." Thesis, University of St Andrews, 1997. http://hdl.handle.net/10023/14085.
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Transformation is a complex multistage process in vitro by which benign cells gradually acquire characteristics of tumour cells. Transformed C3H10T1/2 cells appear in vitro as multilayers of cells termed foci. Two main aspects of transformation of C3H10T1/2 cells in vitro have been investigated. Firstly, the quantitative assessment of the dose and dose-rate effects after irradiation with 250 kVp X-rays were examined and secondly the relationship between various properties of transformed cells in vitro and their tumourigenic potential in vivo. The induction of transformation was found to be linear with dose for 0.25 to 5 Gy X-rays. Lowering the rate at which the X-ray dose is delivered to the C3H10T1/2 cells lowers the observed transformation frequency by at least a factor of two. A variety of transformed phenotypes are observed in vitro and samples of these phenotypes were developed as cell lines and assessed for a number of properties. These properties were the ability to induce tumours in C3H mice and the ability to reconstruct foci in vitro. Other properties examined were growth in vitro parameters (lag time, doubling time and saturation density) as well as chromosome number and distribution. Tumour cell lines were also developed and assessed for the above properties. Transformation phenotypes induced by X-rays and alpha-particles were compared. Differences were found between some of the properties of the X-ray and alpha- particle induced transformants. In particular, higher proportions of X-ray induced transformants were tumourigenic while most of the alpha-particle induced transformants were non-tumourigenic and also tumours induced by the X-ray induced transformants appeared earlier and grew faster than the alpha-particle induced equivalent. The ability of the transformation phenotypes to reconstruct foci in vitro was greater for alpha-particle induced transformants (not including tumour cell lines) than for the X-ray induced transformants. The reverse was true for tumour cells where X-rays produced higher frequencies of reconstructed foci than alpha-particles. No differences were noted in in vitro growth parameters irrespective of transformation phenotype or radiation type apart from differences in saturation density where the transformation phenotypes (not including tumour cells) generally produced higher densities than the tumour cells for both X-rays and alpha-particles. Chromosome numbers in cells of the different transformation phenotypes (including tumour cells) induced by both X-rays and alpha-particles showed a greater spread and a general shift of the mean and modal chromosome number to lower values than that of untransformed C3H10T1/2 cells. The presence of metacentric chromosomes (Robertsonian chromosomes) was not unique to the radiation induced transformation phenotypes as most of the cell lines examined showed fewer of these chromosomes than the untransformed cells. The X-ray induced transformants (including tumour cells) generally produced more Robertsonian chromosomes than the alpha-particle equivalent. Correlation tests of the above properties with tumourigenicity of the transformed cells revealed a positive correlation of tumourigenicity with the ability to reconstruct foci. A negative correlation was noted between the ability to reconstruct foci and the mean and modal chromosome numbers.
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Ali, Abdul Rabbi Manaf. "Regulation of haematopoietic stem cycle (CFU-S) proliferation in irradiated mice." Thesis, University of St Andrews, 1986. http://hdl.handle.net/10023/14074.
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It has been suggested that the proliferation of haematopoietic stem cells (CFU-S) in mice is controlled by the balance of inhibitory and stimulatory factors. In normal mice about 10 percent of the CFU-S population are in DNA synthesis. It has been suggested that a high concentration of inhibitor blocks CFU-S from entering into DNA synthesis. Following damage by cytotoxic agents such as drugs or irradiation about 30 - 50 percent of CFU-S were in DNA synthesis and also stimulator was shown to be present. In this study the entry of CFU-S into DNA synthesis following low and sub-lethal doses of whole body X-irradiation has been studied. Furthermore the stimulator producing cells were also characterized. The number of CFU-S in bone marrow was not affected following exposure to a dose of 0.5 Gy. However the number of committed progenitors for the granulocyte/macrophage lineage was significantly reduced. The percentage of CFU-S in DNA synthesis was found to increase to 37.0+/- 7.0 percent at 30 minutes and 43.9+/-11.2 percent at 2 hours from that observed in unirradiated mice. However at 6 hours the percentage was 14.8 8.1 percent. At a sub-lethal dose of 4.5 Gy, the percentage of CFU-S in DNA synthesis increased to 34.0+/-14.0 percent at 6 hours after exposure, however before this time the percentage remained at a similar level to unirradiated control mice. When plugs of bone marrow were irradiated in-vitro at 0.5 Gy and 4.5 Gy doses, the time of CFU-S entering into DNA synthesis was the same as following in-vivo irradiation. The dose response curve of CFU-S entering into DNA synthesis when measured at 2 hours after exposure showed that the percentage was increased as the dose was increased and reached 30-50 percent at a dose of 0.5 Gy. Above this dose the CFU-S population was not stimulated at this time. When the percentage of CFU-S in DNA synthesis was measured at 6 hours after exposure, the values were the same as control for doses less than 0.5 Gy and above this dose the values were 30-50 percent. The presence of stimulator in bone marrow after irradiation was found to parallel the proliferative activity of CFU-S. The CFU-S population obtained 1 hour after 1.5 Gy was shown not' to respond to stimulator as CFU-S from normal bone marrow dia. The conditioned media prepared from bone marrow of mice Irradiated at 9.0 Gy (1 to 5 days post Irradiation) increased the proportion of CFU-S from normal bone marrow in DNA synthesis to 30-50 percent. The depletion of Thy1.2+ cells from regenerating bone marrow did not affect the ability to produce stimulator. However when Fc+ and Ia-2k+ cells were removed the stimulator production was affected. This suggests that the stimulator producing cells were radioresistant, Thy1.2-, Fc+ and Ia-2k+.
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Chen, Chun-Zhang. "A study of the biophysical mechanisms of damage by ionizing radiation to mammalian cells in vitro." Thesis, University of St Andrews, 1988. http://hdl.handle.net/10023/14081.
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An extensive survey made of published survival data of damage by ionizing radiation to mammalian cells in vitro has led to the new conclusion that the damage is determined by the specific ionization or the mean free path between ionizing events along the charged particle tracks. The optimum damage is observed when the mean free path is equivalent to the DNA double strand spacing of 1.8 nm. Therefore, the biological mechanism of ionizing radiation to mammalian cells in vitro is intra track dominant. A 100 keV electron accelerator has been constructed and commissioned to produce a broad beam irradiation field of greater than 1 cm diameter. The fluence rate may be adjusted from 10 8 cm-2-sec-1 downwards to enable further development as a chronic irradiation facility. Another new feature of the accelerator is that it incorporates a differential vacuum system which permits irradiation of the monolayer cell cultures to be carried out in normal pressure. Experiments of irradiation to Chinese hamster cells, by 241Am alpha particles at low fluence rate, have supplied satisfactory data for testing a new DNA-rupture model which is under development. For V79 cells irradiated at a low fluence rate of 105 cm-2-min-1, when survival data were fitted into the model, new biophysical parameters were extracted and a proposal was made that the repair phenomenon of cellular survival at very low doses is determined by three time factors; the irradiation time, the damage fixation time and the repair time. The values obtained were 3-4 hours for the mean repair time, and more than 10 hours for the damage to be considered permanent. Details of the monolayer cell culture technique developed and used in the present experiments are described. Consideration has been given to the significance of the results obtained from the study in radiation protection and in radiotherapy. In future studies it is recommended that more attention should be paid to measure the ionization events of the radiation studied. Towards the objective of producing a unified dosimeter, more studies are needed to correlate the results for electrons and neutrons for which less data are available. In this thesis the background and the basic theories are introduced in Chapters I and II. Experimental details are described in Chapter III on physical aspects and Chapter IV on biological aspects. Finally the results and discussion are presented in Chapter V.
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Pisani, Carla. "Study of the effects induced by high doses per fraction in radiotherapy: correlations between biological and clinical parameters – the case of intraoperative irradiation of prostate adenocarcinoma." Doctoral thesis, Università del Piemonte Orientale, 2021. http://hdl.handle.net/11579/128008.
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Coghill, Matthew Taylor. "Radiobiological modeling using track structure analysis." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44731.
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The purpose of this thesis is to present data pertinent to and propose conclusions regarding the coordination
of radiobiologic effectiveness (RBE) and linear energy transfer (LET). RBE is a quantity relating the effectiveness
of different radiations in causing cell death. LET is a measure of the rate of energy transferred to material by an
ionizing particle. This relationship of these values varies for different particles. The reason for this is still inconclusive. The petitioner has made use of a toolkit for Geant4, known as Geant4-DNA, to perform track-structure analysis on a chromosome model. Geant4 is an object-oriented program for the "simulation of the passage of particles through matter" developed by CERN that makes use of Monte Carlo methods and is expanded by Geant4-DNA to handle low-energy electron physics as well as physic-chemical effects. The chromosome model, in this case, has been developed by the petitioner as a nucleus with a basic, uniform distribution of chromatin. Radiation damage to DNA, in the form of aberrations, lesions and strand breaks, can be coordinated to energy deposited or number of ionizations occurring in the target (in this case DNA or chromatin fiber). Certain threshold values have been established as indicate of different types of DNA damage. The ultimate goal of this work is to score these clusters of events against the threshold values to determine the severity of DNA damage. The final comparison of the results for different particles will provide for a better understanding of the RBE-LET relationships by improving the understanding of the underlying nanodosimetric qualities.
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Dörr, Wolfgang. "Skin and Other Reactions to Radiotherapy – Clinical Presentation and Radiobiology of Skin Reactions." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133998.
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Clapham, Peter C. "The radiobiology of human colorectal cell lines : an investigation into transformation and radiosensitivity." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265322.
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Dörr, Wolfgang. "Skin and Other Reactions to Radiotherapy – Clinical Presentation and Radiobiology of Skin Reactions." Karger, 2006. https://tud.qucosa.de/id/qucosa%3A27555.
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Pommarel, Loann. "Transport and control of a laser-accelerated proton beam for application to radiobiology." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLX001/document.
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L’accélération de particules par interaction laser-plasma est une alternative prometteuse aux accélérateurs conventionnels qui permettrait de rendre plus compactes les machines du futur dédiées à la protonthérapie. Des champs électriques extrêmes de l’ordre du TV/m sont créés en focalisant une impulsion laser ultra-intense sur une cible solide mince de quelques micromètres d’épaisseur, ce qui produit un faisceau de particules de haute énergie. Ce dernier contient des protons ayant une énergie allant jusqu’à la dizaine de mégaélectron-volts, et est caractérisé par une forte divergence angulaire et un spectre en énergie très étendu.Le but de cette thèse est de caractériser parfaitement un accélérateur laser-plasma afin de produire un faisceau de protons stable, satisfaisant les critères d'énergie, de charge et d'homogénéité de surface requis pour son utilisation en radiobiologie. La conception, la réalisation et l’implémentation d’un système magnétique, constitué d'aimants permanents quadripolaires ont été optimisés au préalable avec des simulations numériques. Ce système permet d’obtenir un faisceau de protons ayant un spectre en énergie qui à été mise en forme, et dont le profil est uniforme sur une surface de taille adaptée aux échantillons biologiques.Une dosimétrie absolue et en ligne a également été établie, permettant le contrôle de la dose délivrée en sortie. Pour cela, une chambre d'ionisation à transmission, précédemment calibrée sur un accélérateur à usage médical de type cyclotron, a été mise en place sur le trajet du faisceau de protons. Des simulations Monte Carlo ont ensuite permis de calculer la dose déposée dans les échantillons. Ce système compact autorise maintenant de définir un protocole expérimental rigoureux pour la poursuite d’expériences in vitro de radiobiologie. De premières irradiations de cellules cancéreuses ont été ainsi réalisées in vitro, ouvrant la voie à l’exploration des effets de rayonnements ionisants pulsés à haut débit de dose sur les cellules vivantesParticle acceleration by laser-plasma interaction is a promising alternative to conventional accelerators that could make future devices dedicated to protontherapy more compact. Extreme electric fields in the order of TV/m are created when an ultra-intense laser pulse is focused on a thin solid target with a thickness of a few micrometers, which generates a beam of highly energetic particles. The latter includes protons with energies up to about ten megaelectron-volts and characterised by a wide angular divergence and a broad energy spectrum.The goal of this thesis is to fully characterise a laser-based accelerator in order to produce a stable proton beam meeting the energy, charge and surface homogeneity requirements for radiobiological experiments. The design, realisation and implementation of a magnetic system made of permanent magnet quadrupoles were optimised beforehand through numerical simulations. It enables to obtain a beam with a shaped energy spectrum and with a uniform profile over a surface with a size adapted to the biological samples.Deferred and online dosimetry was setup to monitor the delivered output dose. For that purpose, a transmission ionisation chamber, previously calibrated absolutely on a medical proton accelerator, was used. Monte Carlo simulations enabled to compute the dose deposited into the samples. This compact system allows now to define a rigorous experimental protocol for in vitro radiobiological experiments. First experiments of cancer cell irradiation have been carried out, paving the way for the exploration of the effects of pulsed ionizing radiations at extremely high dose rates on living cells
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Tran, Chau Vanessa. "Impact d'inhibiteurs de la réparation de l'ADN sur l'interaction tumeur/stroma et impact sur la radiosensibilité." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS321.
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Avec la chimiothérapie et la chirurgie, la radiothérapie fait partie intégrante de l'arsenal thérapeutique pour lutter contre le cancer. Afin de potentialiser l’efficacité des rayonnements ionisants, la radiochimiothérapie s’est développée mais en raison des résultats insuffisants de cette stratégie, de nouvelles voies permettant une modulation de la radiosensibilité tumorale sont évaluées. C’est dans ce contexte d’amélioration de l’efficacité de la radiothérapie que s’inscrit ce travail de thèse. Nous avons évalué l’intérêt thérapeutique de l’association d’inhibiteurs de la réparation de l’ADN à la radiothérapie sur un modèle orthotopique de cancer bronchique et sur un modèle orthotopique de cancer de la tête et du cou. En raison de son rôle prépondérant dans la réparation des cassures simple brin, PARP1 a été ciblé dans un premier temps pour éprouver cette stratégie, à l’aide d’un inhibiteur chimique l’Olaparib. Le rationnel consistait à inhiber la réparation de dommages induits par l’irradiation, pouvant ainsi conduire à la mort des cellules tumorales. Les résultats obtenus in vitro ont montré que l’inhibition de PARP1 permettait en effet de potentialiser les effets de la radiothérapie. Cette association thérapeutique a, par la suite, été évaluée in vivo et a montré une très faible radiosensibilisation, limitée par une toxicité induite par cette association. Afin d’augmenter l’efficacité de cette stratégie thérapeutique, un inhibiteur d’ATR (AZD6738), une des protéines majeures de la réponse aux dommages de l’ADN et au stress réplicatif, a été ajouté à la combinaison initiale. Il a en effet été montré que Chk1, la cible principale d’ATR, était activée dans les cellules traitées avec l’Olaparib et/ou irradiées. Nous avons démontré in vitro et in vivo, que l’AZD6738 améliorait l’efficacité de la combinaison irradiation et Olaparib dans nos deux modèles tumoraux, suggérant le potentiel de cette triple combinaison en clinique. Enfin, en raison du rôle de l’irradiation et de PARP1 dans différents processus immunitaires, nous avons étudié de façon préliminaire l’influence de nos différentes combinaisons thérapeutiques sur l’infiltrat immunitaire tumoral. Sachant que l’efficacité de l’association Olaparib/irradiation avait été démontrée dans des modèles tumoraux implantés en sous-cutané, ce travail de thèse montre l’importance et la pertinence de modèles précliniques plus proches de la pathologie humaine, comme les modèles orthotopiques. En effet, il est très probable que les toxicités observées au cours de ce travail soit la conséquence d’une détérioration avancée des muqueuses présentes dans le champ d’irradiation et que celles-ci ne puissent être observées lors d’irradiation localisée de tumeurs implantées en sous-cutanéWith chemotherapy and surgery, radiotherapy is part of anti cancer therapeutic strategy. To increase ionizing radiations effects, radiochemotherapy has emerged, but because of inefficient results, new pharmacological strategies for modulation of radiosensitization has been assessed. My thesis project is part of this context of improvement of radiotherapy efficiency. We have evaluated therapeutic interest of association of DNA repair inhibitors and radiotherapy on lung cancer model and head and neck cancer model. Because of its implication in single strand break repair, PARP1 has been first, targeted to assess this strategy, with the chemical inhibitor Olaparib. The rational was to inhibit radio-induced damages, leading to cellular death. In vitro, we have demonstrated that Olaparib was promising for enhancing radiation efficacy, but has an in vivo limited radiosensitization, plus we observed with this association a toxicity. Non toxic association has been found by decreasing Olaparib dose, but association efficiency has been limited, meaning that Olaparib, in our model, has a restrained therapeutic index.To increase the efficiency of this combination, we have added an ATR inhibitor (AZD6738), one of the key proteins implicated in response to DNA damages and replicative stress. In fact it has been demonstrated, that ATR main target, Chk1, was activated in Olaparib-treated and/or irradiated cells. We have demonstrated in vitro and in vivo, that AZD6738 improved efficiency of Olaparib and radiotherapy combination in both models, suggesting the potential of this triple combination in clinic.Finally, because of effects of PARP1 and radiation on different immune processes, we have preliminary studied, the influence of this different combinations on immune infiltrate.Knowing that efficiency of the association Olaparib and radiotherapy has already been demonstrated in subcutaneous models, this work has shown the importance and relevance of preclinical models, closer to human pathologies, as orthotopic models. In fact, it is likely that toxicities observed during this work, are the consequence of mucous membrane damaging in the field of irradiation, which cannot be observed with localized irradiation of subcutaneous tumors
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Faizi, M. A. H. P. "The effect of hyperthermia and irradiation on a human ovary tumour xenograft." Thesis, Bucks New University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380292.
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Younis, Abdul-Redha Sahib. "Biophysical damage in metallo-enzyme and mammalian cells by Cu-K X-rays and radioisotopes." Thesis, University of St Andrews, 1989. http://hdl.handle.net/10023/14089.
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In the fields of radiobiology and nuclear medicine there is considerable interest in the important role played by Auger electron cascades caused by inner-shell ionisation in realistic risk. It is necessary to quantify this risk when radionuclides are used on a routine basis as investigative, diagnostic and radiotherapeutic tools, whether the applications involve incorporated electron capture radionuclides or K-shell ionisation of selected stable nuclides by X-rays, as in "photon activation therapy". Relevant published survival data on biological damage caused by the internal emitters 125I, 77Br, 3H, 33P, 131I and 32P which are incorporated into the DNA of mammalian cells, bacteria (E. Coli) and bacteriophages have been collected and the results re-analysed in terms of the parameters of a new damage model to determine an inactivation cross-section for each internal emitter. These quality parameters are the absolute specification of radiation quality and are compared with cross-sections similarly determined for the effects of external radiations from heavy charged particles and photons (chapter 2). The inactivation probabilities obtained for the nuclides 125I, 77Br and 3H extend over a wide range of values depending on the type of nuclide and its distribution, the type of sensitive target and its shape and distribution, and the environmental temperature during both irradiation and post-irradiation incubation. The higher values approach those determined for heavy charged particles with the same mean free path for primary ionisation, and are an order of magnitude larger than would be expected for external irradiation with photon generated electrons. The results for 33P, 131I and 32P nuclides are appreciably smaller than that expected for external irradiation since the long range electrons dissipate most of their energy out of the sensitive target. A theoretical equation for X-ray production by accelerated electrons incident on a thick target has been revised by including factors to compensate for backscattering, direct and indirect ionisation, attenuation in the target and the incident angle of electrons (chapter 3). An electron accelerator X-ray machine capable of delivering monoenergetic photons up to ~ 4.8 gray/sec exposure dose rate from four different targets has been designed, constructed and tested (chapter 4) The biophysical mechanisms of direct and indirect radiation action has also been studied using the metallo-enzyme dihydroorotic dehydrogenase. The enzyme was irradiated both in dry state and in solution at different concentrations and at different dose rates using monoenergetic Cu-K photons from our X-ray machine. A technique was developed whereby it was possible to isolate and quantify each type of radiation action (chapter 5). The inactivation of the enzyme in both solution and in dry state was found to be a single-hit/single-target process. It was also found that in solution the inactivation of the enzyme was dose-rate-and concentration-dependent with efficiency of radical inactivation has an exponential dependence on dose-rate and the inverse of the enzyme concentration. A new model for the inactivation of the enzyme has been suggested and its parameters, namely direct and indirect cross-sections, geometrical cross-section, saturated concentration constant, root mean square diffusion constant, mean free path of radicals absorption, life time and G value of radical production, have been determined. It is expected that this model can be generalised to suit other enzymes (chapter 6).
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Finocchiaro, Domenico <1993>. "Applications of metrological techniques for clinical implementation of dosimetry and radiobiology in molecular radiotherapy." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9250/3/PhD_Thesis_Finocchiaro.pdf.
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Molecular radiotherapy (MRT) is a fast developing and promising treatment for metastasised neuroendocrine tumours. Efficacy of MRT is based on the capability to selectively "deliver" radiation to tumour cells, minimizing administered dose to normal tissues. Outcome of MRT depends on the individual patient characteristics. For that reason, personalized treatment planning is important to improve outcomes of therapy. Dosimetry plays a key role in this setting, as it is the main physical quantity related to radiation effects on cells. Dosimetry in MRT consists in a complex series of procedures ranging from imaging quantification to dose calculation. This doctoral thesis focused on several aspects concerning the clinical implementation of absorbed dose calculations in MRT. Accuracy of SPECT/CT quantification was assessed in order to determine the optimal reconstruction parameters. A model of PVE correction was developed in order to improve the activity quantification in small volume, such us lesions in clinical patterns. Advanced dosimetric methods were compared with the aim of defining the most accurate modality, applicable in clinical routine. Also, for the first time on a large number of clinical cases, the overall uncertainty of tumour dose calculation was assessed. As part of the MRTDosimetry project, protocols for calibration of SPECT/CT systems and implementation of dosimetry were drawn up in order to provide standard guidelines to the clinics offering MRT. To estimate the risk of experiencing radio-toxicity side effects and the chance of inducing damage on neoplastic cells is crucial for patient selection and treatment planning. In this thesis, the NTCP and TCP models were derived based on clinical data as help to clinicians to decide the pharmaceutical dosage in relation to the therapy control and the limitation of damage to healthy tissues. Moreover, a model for tumour response prediction based on Machine Learning analysis was developed.
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Lazarakis, Peter. "Effects of a static magnetic field on biological samples." School of Engineering Physics - Faculty of Engineering, 2009. http://ro.uow.edu.au/theses/3033.
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FTIR spectroscopy uses the absorbed light in an IR beam to determine the composition of a sample. This study was done using FTIR techniques to determine the damage done or alterations caused when a magnetic field was applied to a biological sample (cell cultures).The effects of magnetic fields on biological samples is an area that is not very well understood with little reliable data available.Various experiments investigating the influence of a magnetic field on cell growth, the chemical bonds in cells and the effects during irradiation were performed. Consistently it was seen that the largest changes to the cell were found in hydrogen bonds, most commonly in water. Though perhaps this may not normally create any significant biological impact when a biological sample is irradiated, as in radiotherapy, the chemical and physical structure of water is quite important.
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De, Marzi Ludovic. "Effets physiques et biologiques des faisceaux de protons balayés : mesures et modélisation pour des balayages séquentiels à haut débit." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS546/document.
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L'objectif principal de cette thèse est de développer et optimiser les algorithmes caractérisant les propriétés physiques et biologiques des mini-faisceaux de protons pour la réalisation des traitements avec modulation d'intensité. Un modèle basé sur la superposition et décomposition des mini-faisceaux en faisceaux élémentaires a été utilisé. Un nouveau modèle de description des mini-faisceaux primaires a été développé à partir de la sommation de trois fonctions gaussiennes. Les algorithmes ont été intégrés dans un logiciel de planification de traitement, puis validés expérimentalement et par comparaison avec des simulations Monte Carlo. Des approximations ont été réalisées et validées afin de réduire les temps de calcul en vue d'une utilisation clinique. Dans un deuxième temps, un travail en collaboration avec les équipes de radiobiologie de l'institut Curie a été réalisé afin d'introduire des résultats radiobiologiques dans l'optimisation biologique des plans de traitement. En effet, les faisceaux balayés sont délivrés avec des débits de dose très élevés (de 10 à 100 Gy/s) et de façon discontinue, et l'efficacité biologique des protons est encore relativement méconnue vue la diversité d'utilisation de ces faisceaux : les différents modèles disponibles et notamment leur dépendance avec le transfert d'énergie linéique ont été étudiés. De bons accords (écarts inférieurs à 3 % et 2 mm) ont été obtenus entre calculs et mesures de dose. Un protocole d'expérimentation pour caractériser les effets des hauts débits pulsés a été mis en place et les premiers résultats obtenus sur une lignée cellulaire suggèrent des variations d'efficacité biologique inférieures à 10 %, avec toutefois de larges incertitudesThe main objective of this thesis is to develop and optimize algorithms for intensity modulated proton therapy, taking into account the physical and biological pencil beam properties. A model based on the summation and fluence weighted division of the pencil beams has been used. A new parameterization of the lateral dose distribution has been developed using a combination of three Gaussian functions. The algorithms have been implemented into a treatment planning system, then experimentally validated and compared with Monte Carlo simulations. Some approximations have been made and validated in order to achieve reasonable calculation times for clinical purposes. In a second phase, a collaboration with Institut Curie radiobiological teams has been started in order to implement radiobiological parameters and results into the optimization loop of the treatment planning process. Indeed, scanned pencil beams are pulsed and delivered at high dose rates (from 10 to 100 Gy/s), and the relative biological efficiency of protons is still relatively unknown given the wide diversity of use of these beams: the different models available and their dependence with linear energy transfers have been studied. A good agreement between dose calculations and measurements (deviations lower than 3 % and 2 mm) has been obtained. An experimental protocol has been set in order to qualify pulsed high dose rate effects and preliminary results obtained on one cell line suggested variations of the biological efficiency up to 10 %, though with large uncertainties
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Alkharam, Ali Salem. "Specification of the quality of ionising radiations for unified dosimetry in radiobiology and radiological protection." Thesis, University of St Andrews, 1997. http://hdl.handle.net/10023/13360.
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It is widely agreed in radiobiological and biophysical research that the DNA is the dominant target which can lead to terminal biological damage in the form of cancer or cell death. A main objective in radiation protection is to set the limits of the possible harmful effects to the general population exposed to ionising radiation at low level (environmental level). The initial slope of the dose-response curve is found to be an appropriate parameter to achieve this objective. Bench mark data sets of the initial effects of ionising radiation on cells in vitro were formed which include both physical characterisation of the radiation and the radiobiological parameters. These data-bases include the mammalian cell end-points: cellular inactivation, chromosome dicentrics, HPRT mutations and oncogenic transformations. On the molecular scale, the databases include single-strand and double strand breaks induced in the DNA of both mammalian and non-mammalian cells. Analysis of bio-effect mechanisms of damage to mammalian cells in terms of the quality parameter 'mean free path for linear primary ionisation' for ionising radiation, strongly suggest that there is a common mechanism for the biological endpoints of dicentrics, mutations, and oncogemc transformations. A unified response is obtained for all types of heavy ions and all cells which show: a common inflection point at inter-spacing distance equivalent to lambda0 = 1.4+/- 0.5 nm, a saturation region at lambda < lambda0 and almost constant slope for lambda < lambda0. The lethal lesions are identified as dsb's in the intracellular DNA. It follows that radiation risk factors can be determined on the basis of simple ratios to the inactivation cross sections. The size of these genes are found to be in close proximity to the optimised saturation levels. The probabilities of risk with respect to inactivation, for chromosome dicentrics, oncogenic transformations, and mutations of the HPRT gene are respectively 0.18, 1.6 x 10-4 and 2.91 x 10-5. The same analysis shows that sparsely ionising radiations, which have lower effect cross-sections by an order of magnitude or more, can never reach saturation. Analysis of the molecular dsb's of DNA produced in mammalian cells by heavy ions shows a lower saturation cross-section of 0.83 mum2 which may be compared with the geometrical cross-section of 3.5 mum2. The difference is attributed to a higher packing factor. Calculations using earlier endpoint saturation cross-sections show that 4 dsb's in DNA of a human lymphocyte cell are needed to induce a chromosome dicentric, 100 dsb's in DNA of a C3H10T1/2 cell are needed to inactivate an oncogene, and 3500 dsb's in DNA of a V79 cell are needed on average to delete an HPRT mutant. The feasibility to design a new dosimetric system which would have a unified response, as described above, is considered. NE102A plastic scintillators of 20 mum thickness are found to be a potentially good prospect for detecting weak ionising radiation. By adjusting the concentration of the activator, the mean of the random distance between centres can be modified to simulate the strand-pair distribution of the DNA in mammalian cells. Thus it is possible to simulate the yield of dsb's in DNA damage as those paired centres spaced by about 1.8 nm and to distinguish them from other unwanted pairs of activated sites with different spacings. Using a 60Co-y radiation source, and starting from the knowledge of the equilibrium slowing down spectrum of electrons in plastic scintillator, the yields of photons and paired events with an inter-spacing distance of - 1.8 nm can be calculated. As may be expected, the results show that the combination from the paired events is very small compared to the total scintillation yield but of the same order as that of double strand breaks in mammalian cells. The resulted simulation showed a yield of 10-2 dsb's/keV which is in close proximity with the theoretical result, for a 4 MeV alpha particle, of 7 x 10-3 dsb's/keV. Both the theory and preliminary experimental investigation with a semi-infinite disc of plastic phosphor, 20 mum thick, reveals that the method is potential promising but more detailed study is required on the process for extraction of the desired signal from the practical device.
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Taylor, Graeme C. "The prediction and measurement of microdosimetric spectra relating to neutron cancer therapy." Thesis, University of Birmingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270893.
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Podd, Frank J. W. "Medical X-ray dose reduction including adaptive image processing." Thesis, University of Surrey, 1997. http://epubs.surrey.ac.uk/842724/.
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This thesis investigates possible methods for dose reduction for one of the main contributors to medical x-ray dose, that of fluoroscopic examinations. Background information is provided on the subjects of radiation interaction mechanisms, radiation dose measures, and the health risk from medical x-rays. This illuminates a running theme of the thesis, namely the compromise between image quality and low patient dose. Possible dose reduction methods using both spatial and temporal image processing techniques are investigated. Edge detection is one of the most important sub-components of the spatial image processing system. The commonly used edge detectors are investigated from a theoretical viewpoint and their performances under Poisson noise conditions are compared using receiver operating characteristic analysis. A new metric is suggested for the quantitative comparison of the edge operators under high detection and low false alarm probability conditions. An adaptive pulse dropping control system is created in order to use the image processing sub-systems with low-dose examinations. This control system determines the best x-ray tube pulse-rate based on the amount of movement present in the image. A method of distributing the dose so that areas of high clinical importance have a higher image quality than less important regions is discussed. This method uses a wedge-shaped x-ray beam filter. The problem of varying pixel intensity due to the differing filter thickness is countered by rescaling the image. The various image processing techniques are combined to create a low-dose imaging system. This system achieves a dose reduction of an order of magnitude.
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Coleman, Peter John. "Plasma protein flux across arterial walls in vivo, with relation to atherosclerosis." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307647.
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Marchant, Joanna Katherine. "Soil-to-plant transfer of radionuclides from near surface groundwater : an experimental and modelling study." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268050.
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Kysela, Boris. "Ionizing radiation-induced DNA damage and repair in relation to biological function." Thesis, Brunel University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384841.
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Porssa, Manuchehr. "Synthesis of radiosensitisers targeted to DNA." Thesis, Brunel University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305165.
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Mojiminiyi, Olusegun Ademola. "Studies on radioimmunoscintigraphy with special reference to malignant melanoma, diabetes and endometriosis." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276834.
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Hagger, Josephine Anne. "Evaluation of radionuclide induced damage in marine invertebrates." Thesis, University of Plymouth, 2002. http://hdl.handle.net/10026.1/2483.
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Limited studies have been carried out to assess the potential effects of ionising radiation on marine organisms. Therefore the general aims ofthis thesis were, (a) to assess the cytotoxic, genotoxic and developmental effects of ionising radiation on the embryolarvae of two ecologically relevant marine invertebrates Mytilus edulis and Platynereis dumerilii, (2) to assess the effects of an environmentally relevant cocktail of radionuclides (3) to monitor the potential impact of radiation in the natural environment and finally (4) attempt to predict the potential effects of radiation at a population level. Following validation of developmental stages and mammalian based cytotoxic and genotoxic assays, chromosomal aberrations (Cabs), sister chromatid exchanges (SCEs) and proliferation rate index (PRJ), on the embryo-larvae ofMedulis and P.dumerilii, the embryo-larvae stages were exposed to a reference radionuclide, tritium, (0.37, 3.7, 37 & 370 kBq/ml). Low doses of radiation delivered by tritium were shown to be detrimental to the development of embryo-larvae with an increase in abnormality for P.dumerilii and an increase in mortality for Medulis. Tritium increased the induction of chromosomal aberrations and sister chromatid exchanges, in exposed embryo-larvae, indicating that tritium is potentially genotoxic. Cytotoxic effects (reduction in the cell proliferation rate) were also observed following exposure of embryo-larvae to tritium. In collaboration with the Royal Devonport Dockyard (DML) investigations on the cytotoxic, genotoxic and developmental effects of a cocktail of radionuclides (radioactive liquid waste diluted to 1.8, 3.2, 5.6, 18%) were carried out. All embryo-larvae exposed to 18% radioactive waste were dead within 24h. Both species exhibited increased abnormality, SCEs and Cabs and a reduction in PRJ in dilutions 1.8-5.6%. In general M edulis appeared to be more sensitive to ionising radiation than P.dumerilii embryolarvae. Following experiments on the embryo-larvae stages of the two marine invertebrates studies were carried out to assess the effects of ionising radiation on adult life stages. Following validation of mammalian based genotoxic assays (comet and micronucleus assays) on adult M edulis, the mussels were exposed to a reference radionuclide, tritium, (0.37,3.7,37 & 370 kBq/ml) in an attempt to assess the genotoxic effects of ionising radiation on the adult life stage. An increase in the levels of single strand breaks (comet assay) and in the induction ofmicronuclei (micronucleus assay) in haemocyte cells was observed in adults exposed to tritium. In collaboration with the Royal Devonport Dockyard (DML) a field study was carried out to assess the use ofthe genotoxic assays (comet and micronucleus assays) as biomarkers of exposure to radiation in adult mussels transplanted to an area of radionuclide discharge. Statistical analysis detected no correlation between the health of the deployed mussels and the levels of environmentally realistic radioactivity. After development ofP.dumerilii embryo-larvae to sexual maturity there appeared to be no affect on the number or sex ofthe worms that reached adulthood in comparison to control worms. Although at the highest concentration oftritium (370 kBq/ml) there was a reduction in the number ofeggs produced from sexually matured females. In conclusion, from the current studies it can be stated that ionising radiation is cytotoxic and genotoxic to sensitive embryo-larvae stages ofmarine invertebrates. However further studies need to be carried out to correlate the effects seen at molecular levels with the potential long-term effects observed at population and community levels of these species. 111
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Jones, George Donal Dransfield. "The direct effects of ionizing radiation on DNA and its higher ordered structures." Thesis, University of Leicester, 1987. http://hdl.handle.net/2381/9691.
Full textAbstract:
This thesis investigates the effects of ionizing radiation on frozen aqueous solutions of DNA using e.s.r. spectroscopy and a plasmid (pBR322) strand break assay. To elucidate the mechanisms subsequent to primary ionic radical formation (G˙+ and T˙¯), additives that influence the radiolytic processes were included prior to irradiation. The presence of hydrogen peroxide (Chapter Three) switched the mechanism from direct damage to a pathway in part mediated through oxygen centred radicals (˙OH, HO˙2) and resulted in a modest increase in the number of strand breaks (i.e. radiosensitization). E.s.r. observations showed the appearance of sugar radicals (strand break precursors) which were lost at temperatures well below those of base radicals. The inclusion of a variety of thiols (Chapter Four) resulted in no change to either G˙ + or T˙¯, However, on warming, the normal pattern of radical reactions was dramatically modified, the DNA radical centres being abruptly reduced in concentration. In anoxia this was concomitant with the appearance of RSSR ¯, and strand breaks were noted to decrease (i,e. radioprotection). Under oxic conditions the degree of repair was a function of the relative concentration of oxygen and thiol. E.s.r. indicated repair of DNA centred peroxyl radicals and also RSO˙2 formation. The latter may react with DNA and account for attenuation, by oxygen, of protection afforded by thiols at low concentrations. The effects of ionizing radiation on higher ordered DNA structures (nucleohistone, chromatin and cell nuclei) has been investigated (Chapter Five). Relative to DNA, all systems gave equivalent yields of G˙+, together with protein electron-loss centres (Hist)˙+. However, T˙¯ yields were enhanced, the increase being greatest for nuclei. For the protein component it was suggested that (Hist)˙+ are amide cations, readily trapped by loss of N-H protons, but that the electrons are Mobile and able to transfer to DNA. Mechanisms leading to strand breaks, involving intramolecular hydrogen atom abstraction by directly induced base radicals from neighbouring sugar residues, are proposed (Appendix B) and compared with those obtained for hydroxyl radical damage.
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Vallely, Stephen Ronald. "Radionuclide angiocardiography using a multiwire camera and Tantalum-178." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261943.
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Amoaku, W. M. K. "The effects of ionising radiation on the retina : a clinical and experimental study." Thesis, Queen's University Belfast, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335348.
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Brennan, Patrick Christopher. "Morphological effects of acute and protracted doses of radiation on normal gastrointestinal tract." Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241329.
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Franklin, Paul Anthony. "Zinc and manganese homeostasis in brain." Thesis, University of Sunderland, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283763.
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Hector, Charlotte Lianne. "The impact of patient movement on the delivery of intensity-modulated radiotherapy." Thesis, Institute of Cancer Research (University Of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268887.
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Mobit, Paul Njom. "Monte Carlo and experimental studies of dose measurement in radiotherapy with LiF-TLDs and other solid state dosemeters." Thesis, Institute of Cancer Research (University Of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244763.
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Droughi, Nouri Ali. "Development of high resolution counting techniques for body radioactivity measurements." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241837.
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Carlin, Sean Denis. "The radiotherapeutic potential of the epidermal growth factor receptor." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267078.
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Abdul-Rahman, A. A. L. "Radiolysis of DNA components in aqueous solutions." Thesis, University of Newcastle Upon Tyne, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370873.
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Sakhri, Mohamed. "Radiation protection of protein-A carbohydrate systems." Thesis, University of Salford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315494.
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Metwally, M. M. K. "Radiation induced peroxidation of lipids." Thesis, University of Salford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356180.
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Wakeford, Carol Anne. "Ultrasound and ionizing radiation : a comparison of chemical effects and dosimetry." Thesis, University of Salford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238779.
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Clegg, R. "Radiation-chemical studies of some sulphophthalocyanine complexes and vitamin B12." Thesis, University of Salford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374501.
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