Doctoral Degrees (Radiodiagnosis)

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    The influence of DNA damage, DNA repair and chromatin structure on radiosensitivity
    (Stellenbosch : Stellenbosch University, 2001-12) Roos, Wynand Paul; Bohm, E. L. J. F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiodiagnosis.
    ENGLISH ABSTRACT: The factors which control radiosensitivity are of vital importance for the understanding of cell inactivation and for cancer therapy. Cell cycle blocks, total induced DNA damage, DNA repair, apoptosis and chromatin structure are likely to playa role in the responses leading to cell death. I have examined aspects of irradiation-induced G2/M blocks in DNA damage and repair. In HT29, L132 and ATs4 cells the total amount of induced DNA damage by isodoses of 4.5 Gy, 5 Gy and 2 Gy was found to be 14 %, 14 % and 12 % respectively. Most of the DNA repair was completed before the G2/M maximum and only 3 % of DNA damage remains to be restored in the G2/M block. The radiosensitivity in eleven cell lines was found to range from SF2 of 0.02 to 0.61. By FADU assay the undamaged DNA at 5 Gy was found to range from 56% to 93%. The initial DNA damage and radiosensitivity were highly correlated (r2=0. 81). After 5 Gy irradiation and 12 hours repair two groups of cell lines emerged. The group 1 cell lines restored undamaged DNA to a level ranging from 94 % to 98 %. The group 2 cell lines restored the undamaged DNA to a level ranging from 77 % to 82 %. No correlation was seen between residual DNA damage remaining after 12 hours repair and radiosensitivity. In CHO-K1 cells chromatin condensation induced by Nocodazole was found to marginally increase the radiosensitivity as shown by the change of the mean inactivation dose (D) from 4.446 to 4.376 Gy. Nocodazole also increased the initial DNA damage, induced by 5 Gy, from 7 % to 13 %. In xrs1 cells these conditions increased the radiosensitivity from D of 1.209 to 0.7836 Gy and the initial DNA damage from 43 % to 57 %. Disruption of chromatin structure with a hypertonic medium was found to increase radiosensitivity in CHO-K1 cells from D of 4.446 to 3.092 Gy and the initial DNA damage from 7 % to 15 %. In xrs1 cells these conditions caused radiosensitivity to decrease from D of 1.209 to 1.609 Gy and the initial DNA damage from 43 % to 36 %. Repair inhibition by Wortmannin increased the radiosensitivity in CHO-K1 from a D of 5.914 Gy in DMSO controls to a D 3.043 Gy. In xrs1 cells repair inhibition had no effect on radiosensitivity. Significant inhibition of repair was seen in CHO-K1 at 2 hours (p<0.0001) and at 20 hours (p=0.0095). No inhibition of repair was seen in xrs1 cells at 2 hours (p=0.6082) or 20 hours (p=0.6069). While DNA repair must be allocated to the post-irradiation period, the G2/M block seen in p53 mutants reaches a maximum only 12 hours post-irradiation when most of the repair is completed. As the G2/M block resolves and cells reenter cycle 28 hours after the G2 maximum it appears that repair processes cannot be the only reason for the G2IM cell cycle arrest. At low doses of irradiation initial DNA damage correlates with radiosensitivity. This suggests that the initial DNA damage is a determinant for radiosensitivity. Repair of DNA double-strand breaks by the non-homologous end joining (NHEJ) mechanism, identified by inhibition with Wortmannin, was shown to influence residual DNA damage and cell survival. Both the initial DNA damage and DNA repair were found to be influenced by chromatin structure. Chromatin structure was modulated by high salt and by Nocodazole, and has heen identified as a parameter which influences radiosensitivity.
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    Tuned aperture computed tomography (TACT) : an investigation on the factors associated with its image quality for caries detection
    (Stellenbosch : Stellenbosch University, 2001-03) De Abreu, Murillo Jose Nunes; Nortje, C. J.; Tyndall, D. A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiodiagnosis.
    ENGLISH ABSTRACT: The purpose of this investigation was to explore the multiple variables involved in TACT® image generation in an attempt to optimize this imaging modality for the diagnostic task of primary dental caries detection. The work is divided in seven phases in which the variables are evaluated individually. Teeth from the study samples were mounted in dental stone and imaged with a solid state digital radiography sensor. As a requisite of TACT® imaging, multiple images of the teeth were acquired from different projection angles. These resulting basis images were then used to generate TACT® slices. Variables tested in the investigation included the number of iterative restorations to which the slices were submitted, the number of basis images, the angle formed between the basis images, the two- and three-dimensional distribution of the basis projections in space, and the method through which the slices were reconstructed. For all phases, observers were asked to assess the presence or absence of primary caries in the teeth imaged using the TACT® slices treated with the different variables. Finally, to determine whether the best combination of variables produced a significant improvement in diagnostic performance, a comparison with conventional digital radiography images was carried out. No statistically significant differences were found in caries detection between TACT® slices submitted to different numbers of iterative restorations, reconstructed from basis images bearing different angular disparities, spatial distributions (in both two and three dimensions), or through different reconstruction methods. A statistically significant difference was detected between TACT® slices reconstructed from different numbers of basis projections. The final comparison showed that TACT® was not statistically superior to conventional digital radiography for the task of caries detection. The results of this investigation suggest that, although TACT® has been shown to be useful in many tasks performed in dentistry, its application in caries detection is not essential inasmuch as there are modalities that are simpler, more practical, less expensive, and that submit the patient to smaller radiation doses. Keywords: TACT, tomosynthesis, image reconstruction, digital radiography, caries detection, ROC analysis, analysis of variance