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.
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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)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29375 |
| Date | January 2024 |
| Creators | Desai, Rhea |
| Contributors | Mothersill, Carmel, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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