The requirement of DNA synthesis for the release of Ɣ-radiation-induced mitotic inhibition in mammalian cells has been studied. Mammalian cells in which DNA synthesis had been inhibited by treatment with fluorodeoxyuridine (FUdR) were not released from radiation-induced mitotic inhibition until the FUdR block was removed. After removal of the block, mitotic figures reappeared, but only after a time equivalent to the usual mitotic delay caused by the particular radiation dose employed. This suggests that repair of the mitotic inhibition lesion can not proceed unless the pathway for DNA synthesis is intact. Further evidence for the requirement of DNA synthesis in the release of mitotic inhibition came from the observation of radiation-induced synthesis of DNA during G₂, a stage in the cell cycle normally not associated with such synthesis. / Thesis / Master of Science (MSc)

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The purpose of this thesis is to broaden the tools and knowledge available for understanding the behavior of metals under irradiation to aid in the pursuit of advanced materials for deployment in Generation IV (Gen-IV) nuclear reactor designs. A mean-field study is conducted on a body-centered cubic (BCC) A-B binary metal alloy system. The performance of the simulated metal system is measured by assessing the degree of segregation that occurs at the grain boundary (GB) in the center of the one-dimensional simulation box. This mean-field method was developed using rate theory equations to observe the diffusion of defects and solute atoms in the binary BCC alloy modeled after a section of planes in the <100> direction of α-iron. The method in this thesis is adapted from a previous radiation-induced segregation (RIS) study that was similarly validated against thermal segregation isotherms. This adapted simulation code was used to study RIS by varying the initial values and conditions across ranges relevant to Generation IV reactor designs. The simulations run with this code were centered around segregation energy and the diffusion coefficient relationships between defects and solute atoms. The most influential conditions applied to both the segregation energy and diffusion coefficient relationship test suites were the temperature and dose rate. The interplay of the various segregation energies, manipulated diffusion coefficients, temperatures, and dose rates is explored in this thesis. The code used in this thesis is presented as a modular framework for further parameter study with a clear direction for more complex alloys. / Master of Science / The growing electricity demand for more efficient, safe, reliable, and sustainable means of power generation requires research and subsequent implementation of advanced Generation IV (Gen-IV) nuclear reactor designs. These proposed designs operate under significantly more strenuous conditions from the perspective of materials used in constructing the reactor. Materials inside the reactor will experience temperatures, pressures, and radiation doses greatly exceeding those of previous generations: Gen II through III+. Metals are employed in almost every component inside a reactor and are particularly susceptible to the demanding conditions due to their tendency to lose their ductility under these stressors. This thesis presents a diffusion-based code that models a binary metal alloy under conditions similar to those expected in Gen-IV reactors. The results of the code give insight into the prevalence of a phenomenon known as radiation induced segregation (RIS) in metals under these Gen-IV relevant conditions. The values input into the code have significant effects on the resulting RIS behavior of the metal alloy. This thesis presents correlations between the initial parameters and the amount of segregation this alloy experiences. The results of this thesis allow a sort of mapping of material parameters and operating conditions so that materials can be designed for optimal performance over the lifespan of the next generation of nuclear reactors. The code in this thesis was developed with the expectation that its modularity would be expanded upon to apply to more complex alloys under a broader range of initial conditions.

The BEIR V preferred relative risk models and standard life-table techniques are used to project lifetime fatal cancer risk factors for average members of the Canadian population. Uncertainties associated with projections are evaluated for: (1) sampling variation (statistical error), (2) extrapolation of risks to low doses and low dose rates, (3) projection of excess lifetime cancer risks beyond the current periods of human observation in epidemiological studies, (4) the transfer of site-specific excess risk coefficients between populations with differing baseline cancer rates, and (5) the effect of differences in the age and sex distributions among occupations in the Canadian "radiation" workforce. Results are used to assess the applicability of the fatal cancer risk estimates recommended in ICRP publication 60 to the Canadian population. It was found that sampling variation, extrapolating to low doses and dose rates, projecting excess risks beyond current periods of observation, and the uncertainty in how to transfer site-specific excess risks between populations all cause substantial variations in lifetime cancer risk projections. Site-specific cancer risk projections may be expected to vary by factors of 2 to 5, depending on the source of uncertainty. Site-specific differences were found in the fatal cancer risk factors projected for "average" male and female workers among different occupations in the Canadian workforce. Site-specific worker averages differed by as much as a factor 3. Female average risk factors for digestive cancers were substantially higher than male workers, while male average risk factors tended to be higher for leukemia and respiratory cancer. Overall however, the majority of worker risk factors were within 2.5% of the site-specific projections for the workforce as a whole. The ICRP-60 nominal fatal cancer risk estimates, tissue weighting factors, and lifetime risk projections for prolonged radiation exposure were all in good agreement with equivalent values derived in this report for the Canadian population. In view of the uncertainties, the results suggest the ICRP estimated cancer risks are as good as any presently available and supports the use of the ICRP recommended values for the planning and regulation of radiation protection in Canada. / Thesis / Master of Science (MS)

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Currently, it is very challenging to accurately monitor the response of patients to radiation therapy over the course of treatment. The initial response to ionizing radiation occurs in the cells at a molecular level, and effects of the response are not typically noticeable on short time scales. Surface-enhanced Raman Spectroscopy, or SERS, has proven to be a useful technique in the analysis of tissues and cells at a molecular level. Specifically, the use of targeted SERS probes allows for the detection of specific proteins on the cell membrane. The work presented here looks to assess the feasibility of using targeted SERS probes and two-dimensional SERS microscopy to measure the response of tumour cells to ionizing radiation, by identifying changes in the distribution of membrane proteins following exposure to clinically relevant doses of ionizing radiation (≤ 60Gy). Two different types of targeted SERS probes were investigated, based on the work of Grubisha et al. ([1]; Type I) and Qian et al. ([2]; Type II), both containing a gold nanoparticle core. In a simplified cellular experiment, biotin on the surface of biotinylated OVCAR5 cells was targeted with streptavidin-SERS probes, and the Type-II SERS probes showed the most promising results. However, SERS maps still provided less characteristic spectral signal than expected, and challenges remain in the development of a reproducible cellular imaging technique. Despite difficulties in cellular imaging, the functionality of the Type-II SERS probes was verified separately, using gold slides with a biotin monolayer in place of cells. Following verification, the SERS intensities provided by differently sized clusters of the SERS probes were characterized. To begin, both SERS maps and scanning electron microscope (SEM) images of gold slides were acquired after incubation with Type-II SERS probes for multiple times (1hr, 2hr, 3hr, 12hr). Data analysis of the SEM images provided a measure of the physical distribution of the SERS probes on the surface of the slide, while analysis of the SERS maps provided information about the spectral distribution of the probes. By relating the information provided by the SEM images and SERS maps, a simple polynomial relationship between SERS intensity and the number of clustered SERS probes providing the enhancement was determined, providing a framework for quantifiable SERS imaging. Finally, an independent experiment was devised to ensure that exposure to clinically relevant doses of ionizing radiation would affect the ability of the targeted protein to bind to SERS probes, thus leading to measurable differences in SERS maps of irradiated and unirradiated cells. A series of experiments utilizing the enzyme-linked immunosorbant assay (ELISA) was performed to test the effect of ionizing radiation-induced damage on the ability of streptavidin to bind to biotin, and the results confirmed that a noticeable reduction in binding could be detected at doses as low as 10 Gy. The results of this work demonstrate that following the development of a suitable cell/SERS probe incubation technique, Type-II SERS probes would be appropriate for use in quantifiable SERS imaging. Also, it is suggested that a measurable change in protein function will be present when comparing SERS maps of control cells to those of cells irradiated to clinically relevant doses. / Graduate

Introduction: Some past breast cancer radiotherapy regimens led to an increased risk of death from heart disease. Although heart dose from breast cancer radiotherapy has generally reduced over the past few decades, there may still be some cardiac risk. Estimation of future risk for women irradiated today requires both measurement of their cardiac dose and dose-response relationships, which depend on cardiac dosimetry of past regimens, in conjunction with long-term follow-up data. Methods: Virtual simulation and computed tomography 3-dimensional treatment planning on a representative patient were used to estimate mean heart and coronary artery doses for women irradiated since 1950 in 71 randomised trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview. Patient-to-patient variability in cardiac dose was assessed. Heart and coronary artery doses were also calculated for breast cancer radiotherapy regimens used since the 1950s in Sweden. Cardiac doses from contemporary (year 2006) radiotherapy were assessed for 55 patients who received tangential breast cancer irradiation at a large UK radiotherapy centre. The maximum heart distance (i.e. the maximum distance between the anterior cardiac contour and the posterior tangential field edges) was measured for the left-sided patients, and its value as a predictor of cardiac doses assessed. Results: Mean heart dose for women irradiated in the EBCTCG trials varied from <1 to 18 Gray, and mean coronary artery dose from <1 to 57 Gray. Patient-to-patient variability was moderate. Mean heart dose for women irradiated in Sweden since the 1950s varied from <1 to 24 Gray, and mean coronary artery dose from <1 to 46 Gray. Heart dose from tangential irradiation has reduced over the past four decades. However, mean heart dose for left-sided patients irradiated in 2006 was 2 Gray and around half of them still received >20 Gray to parts of the heart and left anterior descending coronary artery. For these patients, maximum heart distance was a reliable predictor of cardiac doses. For the other patients, mean heart dose varied little and was usually less than 2 Gray. Conclusions: Cardiac doses from breast cancer radiotherapy can be estimated reliably and are now available for use in deriving dose-response relationships in the EBCTCG data and in a Scandinavian case-control study. Cardiac dose has reduced over the past four decades. Therefore the cardiac risk is also likely to have reduced. Nevertheless, for some patients, parts of the heart still receive >20 Gray in the year 2006.

Neste trabalho obtivemos curvas de corrente induzida por raios-x no teflon FEP que apresentou as seguintes características: a) Inicialmente a corrente subiu, atingindo um máximo em torno dos 10s; b) Decaiu lentamente durante aproximadamente meia-hora, e; c) Atingiu um estado estacionário daí por diante. Ao se desligar a radiação, registrou-se a componente atrasada desta corrente. Usamos amostras de 25&#956m de espessura e área irradiada foi de 12,5cm2 ; o campo aplicado da ordem de 104V/cm e taxa de exposição da ordem de 102 R/S. Verificamos que depois de completada de uma medida da corrente induzida num amostra, esta não voltava a se repetir se realizada depois algumas horas; a corrente então não apresentava um máximo, indo diretamente ao valor estacionário; porém se recuperava com o tempo, repetindo a primeira medida depois de algumas semanas. Para mostrar que esta subida e descida da corrente induzida, não era devido a um efeito de campo, realizamos uma medida onde aplicamos o campo intermitente por curtos períodos de tempo, enquanto a amostra era irradiada. O resultado se mostrou igual aos realizados com tensão aplicada permanentemente. Estudamos ainda a dependência da condutividade induzida com a taxa de exposição e com o campo. Finalmente construímos um modelo teórico para o material que permitiu a obtenção de parâmetros do mesmo concordantes com o esperado. Acrescentamos a este trabalho uma curva que mostra o efeito da variação da temperatura sobre uma medida longa da absorção dielétrica. / In this work we measured X-ray indeuced currents in teflon FEP wich show the following features: a) At the beginning the current increases and reaches a maximum at about 10s; b) It decays slowly during 30 minutes, when a steady state is reached slowly during 30 minutes, when a steady state is reached the delayed conductvity was also measured. The sample were 25&#956m thick and the irradiated área was 12,5cm2; the applied field was of the order of 104 V/cm and the dose rate of the order of 102 R/S. It was observed that a new measurement of the induced conductivity does not duplicate the first one, but after a few hours it come backs to the original one. In order to show that the increase and the deacrease of the current is not caused by na electric field effect we realized a measurement where we polled the sample intermitently while it was irradiated. The current thus obtained had about the same values of the first measuments, when the voltage was applied all the time during the measurement. We also measured the absorption current f a teflon sample wich shows after some days the effect of its variation due the variation of the ambiental temperature.