This thesis investigates the effects of ionizing radiation on frozen aqueous solutions of DNA using e.s.r. spectroscopy and a plasmid (pBR322) strand break assay. To elucidate the mechanisms subsequent to primary ionic radical formation (G˙+ and T˙¯), additives that influence the radiolytic processes were included prior to irradiation. The presence of hydrogen peroxide (Chapter Three) switched the mechanism from direct damage to a pathway in part mediated through oxygen centred radicals (˙OH, HO˙2) and resulted in a modest increase in the number of strand breaks (i.e. radiosensitization). E.s.r. observations showed the appearance of sugar radicals (strand break precursors) which were lost at temperatures well below those of base radicals. The inclusion of a variety of thiols (Chapter Four) resulted in no change to either G˙ + or T˙¯, However, on warming, the normal pattern of radical reactions was dramatically modified, the DNA radical centres being abruptly reduced in concentration. In anoxia this was concomitant with the appearance of RSSR ¯, and strand breaks were noted to decrease (i,e. radioprotection). Under oxic conditions the degree of repair was a function of the relative concentration of oxygen and thiol. E.s.r. indicated repair of DNA centred peroxyl radicals and also RSO˙2 formation. The latter may react with DNA and account for attenuation, by oxygen, of protection afforded by thiols at low concentrations. The effects of ionizing radiation on higher ordered DNA structures (nucleohistone, chromatin and cell nuclei) has been investigated (Chapter Five). Relative to DNA, all systems gave equivalent yields of G˙+, together with protein electron-loss centres (Hist)˙+. However, T˙¯ yields were enhanced, the increase being greatest for nuclei. For the protein component it was suggested that (Hist)˙+ are amide cations, readily trapped by loss of N-H protons, but that the electrons are Mobile and able to transfer to DNA. Mechanisms leading to strand breaks, involving intramolecular hydrogen atom abstraction by directly induced base radicals from neighbouring sugar residues, are proposed (Appendix B) and compared with those obtained for hydroxyl radical damage.

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This thesis reports the results of a study of the direct effects of gamma and far UV radiation on nucleic acid model systems. For the gamma study, frozen aqueous solutions of 2'-deoxyribonucleosides were chosen as the model systems which best mimic possible radiation chemical events via the direct effects occuring in DNA in vivo. The low yields and high complexity of the mixtures of degradation products afforded by the direct effects required the development of an efficient analytical procedure. This methodology, once perfected for the most complicated system, that of thymidine, was readily applicable to the study of the direct effects of gamma radiation on other nucleosides and to the study of the direct effects of far UV radiation on thymidine. In Chapter I, we report and discuss the results of the study of the direct effects of gamma radiation on thymidine including the isolation and identification of the chemical modifications induced, and describe experiments designed to probe the mechanisms involved in their formation. In Chapters II and III, we extend the study to other 2'-deoxyribo-nucleosides, 2'-deoxycytidine and 2'-deoxyadenosine. Chapter IV presents the results of the study of the direct effects of far UV light on thymidine, a project designed to complement the gamma study and hopefully to bring additional insight into the mechanisms of formation of those products common to both radiation energies. In particular, the mechanisms of the formation of the spore photoproduct, a lesion known to be formed in DNA in vivo, have been elucidated. The study of the direct effects of gamma radiation on thymidine and 2'-deoxycytidine revealed the formation of several new products. Chapter V reports an analysis of the configurational and conformational properties of these molecules.

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This thesis investigates possible methods for dose reduction for one of the main contributors to medical x-ray dose, that of fluoroscopic examinations. Background information is provided on the subjects of radiation interaction mechanisms, radiation dose measures, and the health risk from medical x-rays. This illuminates a running theme of the thesis, namely the compromise between image quality and low patient dose. Possible dose reduction methods using both spatial and temporal image processing techniques are investigated. Edge detection is one of the most important sub-components of the spatial image processing system. The commonly used edge detectors are investigated from a theoretical viewpoint and their performances under Poisson noise conditions are compared using receiver operating characteristic analysis. A new metric is suggested for the quantitative comparison of the edge operators under high detection and low false alarm probability conditions. An adaptive pulse dropping control system is created in order to use the image processing sub-systems with low-dose examinations. This control system determines the best x-ray tube pulse-rate based on the amount of movement present in the image. A method of distributing the dose so that areas of high clinical importance have a higher image quality than less important regions is discussed. This method uses a wedge-shaped x-ray beam filter. The problem of varying pixel intensity due to the differing filter thickness is countered by rescaling the image. The various image processing techniques are combined to create a low-dose imaging system. This system achieves a dose reduction of an order of magnitude.

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