Thesis (M.Sc.) - Carleton University, 2008. / Includes bibliographical references (p. 93-99). Also available in electronic format on the Internet.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 121-125). Also available via the Internet.

Thesis (M.S.)--University of Michigan, 1965.

Thesis (MTech (Radiography))--Peninsula Technikon, 2004. / Word processed copy. Summary in English. Includes bibliographical references (leaves 101-104). Also available online.

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1940. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 71-78).

Thesis (PhD) - Faculty of Life and Social Sciences, Swinburne University of Technology, 2009. / A thesis submitted in total fulfillment of the requirements for the degree of Doctor of Philosophy, Faculty of Life and Social Science, Swinburne University of Technology - 2009. Typescript. Includes bibliographical references.

This thesis describes a long-term study in which the genetic health of a population accidentally exposed to ionizing radiation of cesium-137. The Goiânia (Brazil) radiological accident of September 1987 involved 249 individuals exposed to doses up to 7 Gy, and included four fatalities. We have investigated the genetic effects of radiation exposure in this population using both cytogenetic and molecular endpoints in T-lymphocytes. The micronucleus assay differentiated between groups exposed to different levels of ionizing radiation. At the molecular level two methods were employed: (1) the hprt clonal assay; and (2) the determination of microsatellite instability. The hprt assay involves in vitro culturing of T-cells and the selection of 6-thioguanine-resistant hprt mutant clones which were then characterized at the molecular level using both RT-PCR and genomic analysis. Exposure to ionizing radiation initially elevated the mutation frequency but this effect gradually diminished, so that 4.5 years no significant increase was observed. This limitation makes the hprt T-cell assay unsuitable for the study of long term past exposure. Analysis of the spectrum of hprt mutations recovered from 10 individuals exposed to relatively high doses of ionizing radiation revealed a significant increase (3.8-fold) in the frequency of A:T → G:C mutations in the exposed group. This increase in A:T → G:C transitions is consistent with the effects of ionizing radiation in prokaryotes and lower eukaryotes and likely reflects the mispairing of radiation-induced thymine, glycol with guanine. In addition, a two-fold increase in the frequency of deletions not readily explained by slippage events and hence which may reflect ionizing radiation-induced DNA strand breakage was also observed. Microsatellite instability was also investigated. Fluorescent PCR and automated DNA sequencer analysis, using genomic DNA from mononuclear cells, were used to investigate the frequency of microsatellite alterations in exposed and non-exposed populations. We examined a total of 200 and 190 alleles respectively and found that the microsatellite instability distribution in the two groups were not different. Our assay lacked sufficient sensitivity to discriminate between spontaneous and induced microsatellite instability and it is, therefore, not suitable for population monitoring. Finally, despite the minimal database, we used the micronucleus and hprt mutant frequency data to estimate the risk associated with radiation exposure for the Goiânia population. The estimated genetic risk for the exposed group was approximately a 24-fold increase in dominant disorders in the first post-exposure generation. Moreover, the risk of carcinogenesis in this population was estimated to be increased by a factor in the range of 1.4 to 1.5 compared to the population at large. / Graduate

Investigating variance in radiosensitivity amongst cell populations contributes to the overall improvement in our understanding of the effects of low dose ionizing radiation. The aim of this thesis was to investigate factors influencing radiosensitivity through analysis of survival curves. The radiation-induced bystander effect and low dose hyperradiosensitivty were observed to help elucidate relationships between these phenomena. First heterogeneity of a cell population was investigated and seven clonal lines of an HCT 116 p53 wild type cell line were derived. Survival curves with a wide range of dose points (0.5 to 15 Gy) were developed and curves were fitted with the linear- quadratic and multi-target models. The McMaster Taylor Radiobiology Cesium-137 source was used for all irradiations in this thesis. Here it was evident that the multi- target model provided a better fit and further analysis revealed a relationship between the curve shoulder and toxicity of bystander effect signals. Clonal lines with a large shoulder size did not show evidence of the radiation induced bystander effect. Since the lowest dose point in curves was 0.5 Gy, a more focused look was taken in the low dose range. iii Survival curves were again produced for all clonal lines adding data to now include six dose points in the low dose region (below 0.5 Gy). Survival curves were re-analyzed with this extensive data set including doses from 0.01 to 15 Gy and now instances of hyperradiosensitivty were evident in all cell lines. The linear-quadratic model did not provide a meaningful fit to the data and so the induced-repair model was used and found to be appropriate in low doses. It was concluded that whether the radiation-induced bystander effect was produced or not, low dose effects such as hyperradiosensitivity may contribute to the overall radiosensitivity of a cell line. Finally, sex of the cell line was investigated using four cell lines. Of the four cell lines, two were included as controls for radiosensitivity. These two cell lines were null for the protein Artemis which assists in the repair of double strand DNA breaks. Thus, when this protein is not functioning as normal, radiosensitivity is induced in the cell line. Through medium transfer bystander effect assays a greater reduction in cell survival was observed in the normal female cell line compared to the normal male cell line. In conclusion, this thesis contributes to the understanding of low dose effects and non-targeted effects of ionizing radiation. Understanding these mechanisms both separately and in combination may contribute to the betterment of radiation therapies and radiation protection. / Thesis / Doctor of Philosophy (PhD)

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