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Title: Antioxidant defence and autoxidative damage in neoplastic disease
Author: Thornley, Andrew Charles
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1987
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The principal factors governing antioxidant defence and lipid peroxidation in vitro have been determined for neoplastic and normal tissues, from mice, bearing Lewis lung carcinomas. These parameters were measured at varying intervals after the intramuscular transplantation of Lewis lung carcinoma cells in C57BL6 mice. The activities of glutathione peroxidase (EC, superoxide dismutase (EC., gamma glutamylcysteine synthetase (EC, and catalase (EC. were similar in tumour tissue to those of lung, the tissue of origin. Glutathione reductase (EC. and glutathione-S-transferase (EC. activities were considerably greater than those of lung. Gamma-glutamyltranspeptidase (EC activity was about 25% of the corresponding value in murine lung. Lewis lung carcinoma tissue contained considerable quantities of lipid peroxide (as determined by the thiobarbituric acid test). The in vitro lipid peroxidation of tumour microsomes was less than that of pulmonary tissue. Tissue from the tumour "core" had significantly greater reduced glutathione concentration, lower mitochondrial superoxide dismutase, glutathione peroxidase and gamma-glutamyltranspeptidase activities, and lower lipoperoxide concentration than the periphery. Glutathione peroxidase, gamma glutamylcysteine synthetase and superoxide dismutase activities from Lewis lung carcinoma cells in monolayer culture (18% O[2] concentration) were greater than those of solid tumour. Histological sections of lung and liver from Lewis lung carcinoma- bearing mice were found to have many pathological changes. The livers of tumour-bearing mice had raised glutathione and DNA concentrations, and increased glutathione reductase, glutathione-S-transferase and gamma-glutamyltranspeptidase activities; hepatic catalase and mitochondrial glutathione peroxidase activities were decreased. Hepatic microsomes from carcinoma-bearing mice had increased thiobarbituric acid-reactivity and were more susceptible to iron/ascorbate lipid peroxidation. Storage, as a suspension in a glycerol-containing phosphate buffer at -80°C, conferred resistance to in vitro lipid peroxidation to liver microsomes from healthy animals, but not to those from tumour-bearing mice. Disturbances in Lewis lung carcinoma-bearing mice could generally only be determined at 9 or more days after tumour cell implantation, when the tumour was just palpable. The livers of genetically obese C57BL6 mice had some similar biochemical characteristics to those of tumour-bearing hosts. Kidney and erythrocytes of Lewis lung carcinoma-bearing mice, and tissues of mice, bearing B16 melanomas, also displayed perturbations of antioxidant defence and lipid peroxidation. The significance of the above observations is discussed. Further experiments are suggested to improve the understanding of the role of autoxidation and antioxidant defence in neoplastic disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available