Made available in DSpace on 2014-10-09T12:33:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:06:16Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2017. / Apoptosis is the dominant mechanism of cell death induced by radiation and is the key mechanism used to remove cells with significant DNA damage. Previous research investigated the feasibility of using the Leukocyte Apoptosis Assay (LAA) to determine individual sensitivity to radiation and it was found that an apoptotic response could be loosely linked to age, race and gender. Apoptosis is controlled by the Bcl-2 proteins and therefore the balance between Bax and Bcl-2 protein expression is important. With this background it would be relevant to know why certain individuals are more sensitive to radiation than others. The objectives of this study was to evaluate the effect of ionising radiation on apoptotic proteins, Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) expression and to explore if there is a relationship between radiation induced apoptosis (RIA) and Bcl-2 or Bax expression.

A formação de pares e ANTPOT._ hPOT.+ é o efeito imediato da ação da radiação sobre a matéria. Nos vidros boratos sem impurezas, os elétrons liberados durante o processo de irradiação são capturados por estados metaestáveis das vacâncias de oxigênio cujos níveis estão distribuídos em torno de uma profundidade média de aproximadamente 0,2eV abaixo da base da banda de condução. Nessas vacâncias são formados os centros de elétrons do boro (BEC). Os buracos correspondentes deixados na banda de valência se estabilizam em sítios de oxigênio que ligam átomos de boro tri-coordenados a átomos de boro tetra-coordenados, formando assim os centros de buracos boro-oxigênio (BOHC), com energia de aproximadamente 1,0eV acima do topo da banda de valência. Nos vidros boratos com baixa concentração de impurezas, tais como o ferro e hidrogênio, comumente encontradas em muitas amostras, uma parcela específica dos elétrons e buracos produzidos pela irradiação é neutralizada por íons dessas impurezas, sob condições que dependem da afinidade química e do estado de oxidação do sistema. Com isso, as concentrações de BEC e BOHC diminuem imediatamente após a irradiação da amostra. Como os vidros boratos são bons isolantes elétricos, espera-se que cada par (BEC POT. -, BOHC POT. +) se forme a partir de átomos que sejam primeiros ou segundos vizinhos na matriz vítrea estando, portanto, a uma distância suficientemente pequena para formarem dipolos elétricos metaestáveis. A mesma hipótese vale para o caso envolvendo impurezas onde, por exemplo. o par ([Fe POT. 2+]POT. -, BOHC POT. +) formaria também um dipolo elétrica local metaestável. Em nosso trabalho usamos a técnica de análise de impedância para estudar a presença desses dipolos em vidros previamente expostos à radiação ionizante. Estudamos os vidros Al IND. 2 O IND. 3.3BaO (Ax) e 2/7(100-x)Al IND. 2 O IND. 3.5/7(100-x)B IND. 2O IND. 3.xBaO (Bx) (mol %), ) onde x é a porcentagem de álcali no vidro. Determinamos experimentalmente as constantes dielétricas epsilon dos vidros Ax (para x=30) Bx (para x=20, 30 e 40) e comparamos os resultados. Constatamos que o vidro B20 apresenta uma curva de resposta em baixas freqüências que indica uma relaxação dipolar bem acentuada em relação aos demais vidros. Observamos também, através de nossos espectros de impedância, a presença de dipolos elétricos induzidos por raio x. / The immediate effect of the action of the ionizing radiation on the matter is the formation of e-h+ pairs. For the borate glasses free of impurities the electrons released during the irradiation process are trapped by metastable states of oxygen vacancies whose levels are distributed among an average value of about 0.2 eV below the bottom of the conduction band. At these vacancies the formation of boron electron centers (BEC) take place. The holes left in the valence band are stabilized at the oxygen sites bridging tri-coordinated to tetra-coordinated borons, fonning the boron-oxygen hole centers (BOHC) with average energy of about 1.0 eV above the top of valence band. In borate glasses with low content of impurities such as iron and hydrogen that are often found in most samples, a specific fraction of the electrons and holes are scavenged by the ions of these impurities, under conditions that are dependent of the chemical affinity and of the oxidation state of the system. As a consequence, the BEC and BOHC concentrations decrease immediately after the sample irradiation. As the borate glasses are good electrical insulators, it is expected that each pair (BEC-, BOHC+) be formed from atoms occupying the first or second nearest neighboring sites in the glassy matrix so that the distance among them is sufficiently small to the metastable electrical dipoles being formed. The same hypothesis is valid for the case involving impurities where, e.g. the ([Fe2+], BOHC+) pair is a local metastable electrical dipole. In this work the technique of impedance analysis is applied to study the presence of these dipoles in glasses previously submitted to the ionizing radiation. We studied the glasses of composition Al2O3.6B2O3.3BaO (Ax) and 2/7(100-x)Al2O3.5/7(100- X)B2O3.xBaO (Bx) (mol %), where x is the alkali percent fraction in the glass. Experimental evaluation of dielectric constants \' was performed for the Ax (x = 30) and Bx (x = 20, 30 and 40) and the results were compared. It was found that the B20 glass shows a feature that indicates a greater dipolar relaxation as compared with the other samples. It was demonstrated, also by impedance spectroscopy, the presence of dipoles induced by x-ray.

M.Sc. (Biochemistry) / Please refer to full text to view abstract

Clinical studies suggest radiation dose and dose rate cause increased failure of medical implants however, little evidence supports this claim and due to the complexity of an in vivo environment, separating variable implants is difficult. Before beginning to understand material changes in vivo, a systematic study of silicone and polyurethane exposed to radiation is needed to verify whether radiation is a major variable contributing to material changes. This research fills a gap within the current literature by investigating low dose therapeutic radiation and varying dose rates at sterilization dose and answers questions on whether radiation in an aqueous environment alone is enough to significantly alter material properties. This is the first research to apply a water environment to therapeutic doses and the first to investigate a range of dose rates for clinical applications. Biomedical grade silicone and polyurethane films will be exposed to both types of radiation in an aqueous environment separately and analyzed for changes. The limited current literature combined with standards for biomedical devices will be used to characterize changes seen in materials. The first strategy used to explore the compliance of biomedical grade polymers employs low doses of therapeutic radiation ranging between 0 Gy and 80 Gy. Analysis of these low doses results in confirming cellular, mechanical and chemical stability of silicone and polyurethane. The second strategy used to investigate silicone and polyurethane exposed materials to 25 kGy (sterilization dose) of gamma irradiation at varying dose rates (3.2 - 833 Gy/min). Results from these studies conclude that varying the dose rate causes slight changes in both materials but not significant enough to alter bulk material properties. In conclusion, the results from this research reveal that both silicone and polyurethane maintain their stability at low doses and varying dose rates of irradiation while in an aqueous environment. This indicates that increased failure rates seen in silicone and polyurethane materials in vivo when exposed to radiation cannot be contributed to radiation alone. With the highly complex environment medical devices are exposed to in vivo, each variable that may contribute to failure should be investigated individually before combining to fully understand the mechanisms of material failure. This study indicates that the environment may play a larger role in material change and there is a need for updates to medical device standards. / PHD / Clinical studies suggest radiation dose and dose rate cause increased failure of medical implants however, little evidence supports this claim and due to the complexity of a human environment, separating factors contributing to failure is difficult. Before beginning to understand material changes, a study of silicone and polyurethane exposed to radiation is needed to verify whether radiation is a major variable contributing to material changes. The results from this research reveal that both silicone and polyurethane maintain their stability at low doses and varying dose rates of irradiation while in water environment. This indicates that increased failure rates seen in silicone and polyurethane materials in clinical settings when exposed to radiation cannot be contributed to radiation alone. With the highly complex environment medical devices are exposed, each factor that may contribute to failure should be investigated individually before combining to fully understand the mechanisms of material failure. This study indicates that the environment may play a larger role in material change and there is a need for updates to medical device standards.

No description available.

<p> This study is one of the first to examine non-targeted effects of radiation in fish cell lines, with the aim of identifying a reliable reporter system for evaluating radiation damage in fish. The ability of the fish cell lines to clone was determined as the clonogenic assay was a major end point used to measure survival. A direct survival curve was completed for all cell lines that were deemed clonogenic using a cobalt-60 γ-radiation source. Non-targeted effects of radiation were evaluated by conducting bystander experiments on all fish cell lines. Delayed Cell Death (DCD) experiments were completed on the fish cell line that showed evidence of a cell death associated bystander effect as these phenomena may be linked. Four of the eight cell lines were found to be clonogenic. The cell line, RTG-2, was found to be the most radiosensitive at lower doses. All of the clonogenic cell lines, with the exception ofRTG-2 cells, generally showed increased Plating Efficiency (P.E.) when Irradiated Cell Conditioned Media (ICCM) was tested on unirradiated autologous cells. ICCM from the clonogenic and non-clonogenic cells was also tested on the mammalian cell line. This resulted in increased cell survival, with the exception of the RTS-pBk+ (p<O.OOl), RTS-34st (p<O.Ol) and ZEB 2J (p<0.05) cell lines. Since RTG-2 showed the most prominent cell killing bystander effect, DCD experiments were performed on this cell line. DCD was found in the progeny of irradiated parental cells at all doses tested. Cell kinetics also showed the generation of possible DCD. The results show that both bystander signal production and cellular responses vary depending on the cell line and that DCD and bystander effects are tentatively linked through genomic instability. The RTG-2 cell line may be a suitable model for a reliable reporter system to aid in determining the nontargeted effects of radiation in fish in the environment. </p> / Thesis / Master of Science (MSc)

It is has been observed in several cell systems that cisplatin can radiosensitize and that the response of cells to combination cisplatin and radiation depends on several factors. These include the radiation dose and drug concentration used, the order in which the two treatments are administered, and the time between their administration. The response of a head and neck squamous carcinoma cell line to combination cisplatin-radiation treatment was examined. The response was found to be additive when cisplatin was given first, regardless of the timing and magnitude of the treatments administered. When cells were treated with radiation first, antagonism was observed for low radiation doses and drug concentrations. The response may be explained by a low radiation dose induction of processes that protect the cell from a second damaging agent, similar to the adaptive response. There is some indication in the literature that cisplatin can preferentially radiosensitize cells that are proficient in certain types of DNA repair. Therefore, the response of a cisplatin-resistant strain of the SCC-25 cell line was also investigated. The cisplatin-resistant cell line was found to be substantially radiosensitized by cisplatin for moderate amounts of radiation and cisplatin. The results are discussed with reference to the current proposed mechanisms for cisplatin-radiation interaction. / Thesis / Master of Science (MS)

Diagnostic radiation is typically avoided during pregnancy, as the effect of low-dose radiation exposure on the fetus is uncertain. The objective of this study was to determine if ionizing radiation exposure during late fetal development would cause an adverse intrauterine environment, and lead to growth restriction of offspring and a hypertensive phenotype later in life. To study this, pregnant BALB/cJ mice were exposed to ionizing radiation at 5, 10, 50, 100, 300 or 1000 mGy on gestational day 15. Offspring were weighed weekly from the age of weaning until a mature age of 16 weeks. Cardiovascular effects were assessed every other week via heart rate and blood pressure measurements using tail plethysmography. The expression of genetic markers for endothelial dysfunction, inflammation, mitochondrial capacity, and regulation of the oxidative stress response in the aorta and heart for the 1000 mGy was assessed from tissue collected at 17 weeks of age. We observed no effects of low to mid dose (5-300 mGy) radiation on offspring growth and blood pressure. Growth restriction was observed in male and female offspring exposed to high-dose radiation (1000 mGy). In the heart, there was no observed effect on mitochondrial capacity and oxidative stress response genes. In the aorta, we observed decreased TNF-α expression in male offspring, which may be linked to the growth restriction but was not considered a sign of cardiovascular dysfunction. There were no observed effects of exposure to 1000 mGy on cardiovascular function. This study provides knowledge on the possible effects of radiation on in utero development, which broadens the knowledge on the range of stressors capable of affecting offspring growth and development. / Thesis / Master of Science (MSc)

<p> In spite of the difficulties involved in molecular and cellular studies of antibiotic-free cultures of primary human cells, investigations of the sedimentation and survival properties of cell cultures derived from Xeroderma Pigmentosum patients were successfully carried out. Emphasis was on the cellular and molecular effects of ionizing radiation; however preliminary data for cell survival after exposure to UV was obtained.</p> / Thesis / Master of Science (MSc)