The introduction consists of a review of the current evidence concerning the effects of near-ultraviolet radiation on cells, with particular emphasis placed upon possible effects on cell membranes. The experimental work, the broad aim of which is to expand existing knowledge of the effects of near-ultraviolet radiation that may lead to cell lethality, has centred upon the irradiation of a DNA repair-proficient Escherichia coli K-12 strain, SR385, using both monochromatic and broad-band sources. The work is divided into five parts. Chapter 1 indicates that broad-band near-ultraviolet irradiation of SR385 induces a sensitivity to inorganic salt, which is largely recoverable by holding treated cells in a complex recovery medium. By using various metabolic inhibitors, the recovery process has been related to a return of normal membrane functions. Chapter 2 describes an action spectrum, from 254-405nm, for ultraviolet radiation-induced salt sensitivity, and shows that this effect is important only at wavelengths above 310nm. The third part of the experimental section describes a more direct means of measuring ultraviolet radiation-induced membrane damage by the detection of leakage of radioactive labels from treated cells. An action spectrum, from 254-405nm, determined for 86 rubidium leakage, indicates that membrane damage may be important in near-ultraviolet (but not far-ultraviolet) radiation-induced cell lethality. Chapter 4 describes the effect of the phase of growth of the cell in determining its senstivity to near-ultraviolet radiation. The final chapter comprises a preliminary investigation into the effects of membrane damage in influencing the assessment of mutagenesis by near-ultraviolet radiation, by reversion to prototrophy. The data obtained in each section have been discussed in the context of current published concepts regarding the induction and repair of damage in cells by ultraviolet radiation.

The introduction includes a review of the current knowledge of the cellular effects of ionizing radiation and the role of sensitizers in modifying these effects. The experimental part, the broad aim of which is to gain an insight into the mechanism of ionizing radiation induced inactivation and mutagenesis, is divided into three parts. The first part is concerned with the study of the oxygen enhancement of gamma inactivation in the double mutant Escherichia coli K-12 AB 2480 uvr A rec A, and the evaluation of the role of superoxide dismutase enzyme and sulphydryl groups in this process. In the second part, the effect of three classes of sensitizers, the nitroxyl compounds TAN and TMPN, the electron affinic compounds PNAP and misoni-dazole and the sulphydryl binding agent NEM on the inactivation of Escherichia coli K-12 AB1886 uvr A by gamma radiation was studied. The final part comprises a comparative study of the mutational response of ABl886 following gamma irradiation in the presence of sensitizers. The data obtained in each part have been discussed in the context of the current concepts and in comparison with the published work.

The introduction includes a review of the evidence which links exposure to the ultraviolet component of sunlight with the induction of skin cancers in humans and of the use of model cellular systems to study the induction and repair of damage in cells induced by far, mid and near ultraviolet radiations. Particular emphasis is placed on the use of human cell strains cultured from individuals with rare genetic disorders involving characterised or putative DNA repair defects, associated with an increased incidence of malignant disease. The experimental work is in three parts. The first is concerned with the characterisation of the responses of normal human skin fibroblasts to inactivation by monochromatic wavelengths in the far, mid and near regions of the ultraviolet spectrum. The second part of the experimental work takes the form of a comparative study of the responses of cell strains derived from individuals with the rare genetic disorder, ataxia-telangiectasia, and normal cells to inactivation by far, mid and near ultraviolet radiations. The final part of the experimental work comprises a study of the inactivation of normal and xeroderma pigmentosum human skin fibroblasts by seven monochromatic wavelengths between 254 nm and 365 nm. From these data action spectra have been determined for the inactivation of the two cell strains. The data obtained in each section have been discussed in the context of current concepts regarding the induction and repair of damage in cells by ultraviolet radiation and their biological consequences for the cell and by extrapolation for the whole organism.

No description available.

The aim of the first part of this thesis (Chapter 1, 2 and 3) is based on the chemiluminescence probing (CLP) applications as a technique to study the redox metabolic activity of Ehrlich Ascites tumour cells (EAT). Lucigenin was introduced as a non-isotope substrate label. Lucigenin CL result from reductive oxygenation, involves two electrons reduction reactions. Lucigenin can serve as substrate in an oxygen-redox reaction, yielding electronically excited N-methyl acridone as a product. Chapter 4 deals with the effect of nitroimidazole agents on the CL of EAT cells plus lucigenin and on their redox activity. The ability of the nitroimidazole compounds to accept electrons makes these drugs mimic oxygen, and have possible involvement of free radical intermediate in the electron transfer processes of EAT cells. The electron affinity have provided the basis for the nitroimidazole in chemotherapy, i.e. potential for radiotherapy. Chapter 5 deals with the combination action of hyperthermia (HT) and pharmacological treatment of EAT cells, investigated by means of CL. This chapter is devoted to study the thermal tolerance and redox activity of EAT cells in the presence and absence of 5-nitroimidazole using CLP techniques. A biochemical agent, lucigenin, is used as the probe label. The aims of Chapters 4 and 5 are to - 1. evaluate the effect of HT alone on EAT cells in vitro, 2. investigate the cytotoxic effect of nitroimidazole particularly 5-nitroimidazole together with HT, 3. study the influence of thermal tolerance on cell killing by 5-nitroimidazole. 4. study the effect of timing and order of administration of HT and 5-nitroimidazole in vitro. HT can increase the therapeutic effectiveness of the hypoxic drug sensitizer as a selective agent inteferring with cellular respiration and formation of metabolites which accumulate in cells. HT is likely to effect cellular electron transfer within cells and may accelerate the processes. Sensitizer will undoubtedly serve as a marker for cancer hypotic cells in studies of tumour and tumour cell kinetics and might have a role in cancer diagnosis and therapy. The second part of the thesis (Chapter 6) covers the lyoluminescence (LL) techniques (i.e. emission of light on dissolution of irradiated solids) in the study of the dosimetric problem of internally incorporated β-emitter in tissue equivalent saccharides and amino acids. The third part of the thesis (Chapter 7) covers the possible dosimetric application of piezoluminescence (i.e. emission of light from crystals subjected to pressure of irradiated solid crystal) in alkali halides irradiated with γ-rays and the possible mechanism of piezoluminescence (PL). In this investigation, crystals of NaCl, KBr and KCl were used. In addition, standard LiF chips (TLD-100), CaF₂-(Dy) (TLD-200) and CaF₂ with different impurities of an alkaline earth halide were used. The lower limit of doses (0.25 Gy) was limited by the amount of produced light. It is conceivable that with specially prepared crystals, containing controlled impurities and optimized for a PL readout, the range of doses could be extended down.

No description available.

No description available.

No description available.

No description available.

Limited studies have been carried out to assess the potential effects of ionising radiation on marine organisms. Therefore the general aims ofthis thesis were, (a) to assess the cytotoxic, genotoxic and developmental effects of ionising radiation on the embryolarvae of two ecologically relevant marine invertebrates Mytilus edulis and Platynereis dumerilii, (2) to assess the effects of an environmentally relevant cocktail of radionuclides (3) to monitor the potential impact of radiation in the natural environment and finally (4) attempt to predict the potential effects of radiation at a population level. Following validation of developmental stages and mammalian based cytotoxic and genotoxic assays, chromosomal aberrations (Cabs), sister chromatid exchanges (SCEs) and proliferation rate index (PRJ), on the embryo-larvae ofMedulis and P.dumerilii, the embryo-larvae stages were exposed to a reference radionuclide, tritium, (0.37, 3.7, 37 & 370 kBq/ml). Low doses of radiation delivered by tritium were shown to be detrimental to the development of embryo-larvae with an increase in abnormality for P.dumerilii and an increase in mortality for Medulis. Tritium increased the induction of chromosomal aberrations and sister chromatid exchanges, in exposed embryo-larvae, indicating that tritium is potentially genotoxic. Cytotoxic effects (reduction in the cell proliferation rate) were also observed following exposure of embryo-larvae to tritium. In collaboration with the Royal Devonport Dockyard (DML) investigations on the cytotoxic, genotoxic and developmental effects of a cocktail of radionuclides (radioactive liquid waste diluted to 1.8, 3.2, 5.6, 18%) were carried out. All embryo-larvae exposed to 18% radioactive waste were dead within 24h. Both species exhibited increased abnormality, SCEs and Cabs and a reduction in PRJ in dilutions 1.8-5.6%. In general M edulis appeared to be more sensitive to ionising radiation than P.dumerilii embryolarvae. Following experiments on the embryo-larvae stages of the two marine invertebrates studies were carried out to assess the effects of ionising radiation on adult life stages. Following validation of mammalian based genotoxic assays (comet and micronucleus assays) on adult M edulis, the mussels were exposed to a reference radionuclide, tritium, (0.37,3.7,37 & 370 kBq/ml) in an attempt to assess the genotoxic effects of ionising radiation on the adult life stage. An increase in the levels of single strand breaks (comet assay) and in the induction ofmicronuclei (micronucleus assay) in haemocyte cells was observed in adults exposed to tritium. In collaboration with the Royal Devonport Dockyard (DML) a field study was carried out to assess the use ofthe genotoxic assays (comet and micronucleus assays) as biomarkers of exposure to radiation in adult mussels transplanted to an area of radionuclide discharge. Statistical analysis detected no correlation between the health of the deployed mussels and the levels of environmentally realistic radioactivity. After development ofP.dumerilii embryo-larvae to sexual maturity there appeared to be no affect on the number or sex ofthe worms that reached adulthood in comparison to control worms. Although at the highest concentration oftritium (370 kBq/ml) there was a reduction in the number ofeggs produced from sexually matured females. In conclusion, from the current studies it can be stated that ionising radiation is cytotoxic and genotoxic to sensitive embryo-larvae stages ofmarine invertebrates. However further studies need to be carried out to correlate the effects seen at molecular levels with the potential long-term effects observed at population and community levels of these species. 111