Doctoral Degrees ( Radiobiology)

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Browsing Doctoral Degrees ( Radiobiology) by Subject "Radiosensitivity"

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    Evaluation of the effect of radiofrequency electromagnetic waves on radiosensitivity
    (Stellenbosch : Stellenbosch University, 2019-12) Chinhengo, Angela; Akudugu, J. M.; Serafin, A. M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiobiology.
    ENGLISH SUMMARY : Cancer is a major cause of human death worldwide, and one of the very real challenges is how to control treatment resistance. An additional challenge is the co-morbidity of cancer, with certain infections complicating its management. Radiotherapy (RT) is considered the first line of treatment for most superficial cancers, as these malignancies tend to respond well to radiation. The use of hypofractionated treatment may be beneficial for certain tumours, but hypofractionation may result in severe side-effects from normal tissue toxicity from which the patient may not recover. To circumvent this, radiation modifying agents that potentiate the tumour inactivating effects of ionising radiation and thereby lead to a reduction in radiation dose and prevent normal tissue toxicity, can be utilised. Magnetic fields have long been suggested as potential enhancers of radiation effects. Studies on the combined biological effects of radiofrequency fields (RFF) and ionising radiation are virtually non-existent. The use of RFF adjuvant to radiotherapy may be beneficial, as they have been shown to exhibit in vitro radiosensitising and radioprotective effects in malignant and normal cells, respectively, with the possibility of a significant dose reduction. There is, however, a need to understand the mechanisms by which these RFF influence radiosensitivity so that they can be employed efficiently as radiotherapy modulators. The main goal of radiotherapy is to kill tumour cells and spare normal tissue, and a good modifying agent would be one that sensitises the tumour whilst protecting normal tissue. This study assessed the effect of radiofrequency fields (RFF), modulated at 100, 1000, 2000 and 4000 Hz, on the radiosensitivity of four cell lines: a p53 mutant melanoma cell line, MeWo; a p53 wild-type melanoma cell line, Be11; a p53 mutant prostate cancer cell line, DU145; and a p53 wild-type normal lung fibroblast cell line, L132. The radiomodulatory effect of radiofrequency fields was evaluated using the colony assay. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD) and micronucleus assays were used to assess the possible mechanisms by which radiofrequency fields influence the radiosensitivity of cells. The data demonstrate that radiofrequency fields are more efficient in modulating large fractional doses of X-rays and could find application in hypofractionated radiotherapy as adjuvants, especially for tumours with low alpha/beta ratios. This can have a positive impact on the management of patients with superficial tumours that may be resistant to low fractional doses of radiation. Radiofrequency fields modulate cellular radiosensitivity in a frequency- and cell type-dependent manner and their effects appear to be linked to p53 status. Cellular responses such as metabolism, DNA damage processing (based on micronuclei formation), and abnormal proliferation (based on binucleation) seem to be underlying factors mediating the radiomodulatory effects of radiofrequency fields. Mechanisms by which radiofrequency fields can possibly modulate radiosensitivity are: amplification of radiation-induced genotoxicity, cell cycle arrest, and disturbance of other cellular biochemical processes that lead to alteration of homeostasis. Alternative ways by which RFF affect radiosensitivity are: interfering with the synthesis and function of charged proteins in the cell leading to programmed cell death or premature cell ageing, perturbation of intracellular calcium ions which can trigger apoptotic or necrotic cell death, and/or modulating the expression of Bcl-2 family proteins. Given this complexity, a potential use of radiofrequency fields as a non-invasive therapeutic modality would require standardisation to establish reproducibility. A more detailed understanding of how radiofrequency fields interact with ionising radiation would also prove beneficial in the broader field of radiation protection.