Peters, LindaGoodall, Renëe Jo-Leigh2026-08-182026-08-182026https://hdl.handle.net/10289/18551This research is a key part of a Phase 1(b) clinical trial that was designed to investigate a potential therapeutic dose of selenium (Se) in an oncology setting to aid in protection against toxicities caused by cancer therapies. The trial's primary objectives were to identify the most effective combination of Se dosage (1600 or 6400 μg/day) and compound using three forms of Se (Selenomethionine (SLM), methyl-selenocysteine (MSC), and Sodium selenite (SS). To achieve this, western blot methodologies were used to investigate the effect of the Se compounds on the protein expression. Three antibodies, HIF-1α, EGLN1 and EGLN3 were used to identify changes in the hypoxic pathway, CASPASE-8 was used for the apoptosis pathway and a singular GAPDH loading control was used to estimate regulation change. In addition, LORD-Q PCR was implemented to evaluate both the mitochondrial and nuclear DNA damage. Nine patients who provided informed consent were recruited for the trial. The trial protocol involved seven visits in which blood and plasma samples, adverse events (AE) reporting, and other safety procedures were collected. Two baseline (at the pre-check visit and on day 1) samples were taken one to two weeks apart before dosing to assess intrapatient variability. Two samples for 1600 μg and 6400 μg and a singular post-trial sample over the course of the 12 week trial. Patients kept a diary to self-record any AEs experienced over the trial period. No AEs higher than grade 2 were reported during the trial, with the most common AE being gastrointestinal-related. Western blot analysis showed minimal increase in expression for HIF-1α for four out of five patients with data, when compared to the baseline samples and showed an overall decreased protein expression when normalised against GAPDH. Except patient 29 who showed a distinct increase during the trial, peaking at 25 times the level of GAPDH. Themeasurement of the apoptotic pathway using CASPASE-8 was used however, insufficient data was gained. LORD-Q PCR data showed that damage sustained to mtDNA and ntDNA was not consistent between patients of a singular compound. Data from this trial demonstrate a potential protective effect on DNA damage at the nuclear and mitochondrial level at both 1600 μg/day and 6400 μg/day in all Se compounds. MSC and SS showed to be the least volatile compounds, indicating increased protective effects against DNA damage, which is supported by the western blots for hypoxia. SLM was volatile, showing higher mitochondrial damage and a slight upregulation in the minimal apoptosis data obtained. The difference in in protective effects and pathway regulation was minimal; further investigation into the hypothesis that they are at the same level in the U-shaped tolerance that Se has in humans is advised. Future studies should further investigate the clinical significance and potential of Se as an adjuvant therapy alongside chemotherapy and radiotherapy in cancer patients.enAll items in Research Commons are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.Thesis