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Title: Glutathione S-transferases in the pancreas
Author: Hayes, Peter C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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Glutathione S-transferase (GST) is an important xenobiotic metabolising enzyme which has been extensively studied in the liver. In the first part of this study immunohistochemistry was used to identify the presence and histological localisation of different GST isoenzymes in various gastrointestinal tract tissues in the human in health and disease. GSTP was found throughout the gastrointestinal and biliary tract whilst the position and quantity of other isoenzymes varied locally. Increased expression of GSTP was observed in cholangiocarcinoma and colonic adenocarcinoma, but not hepatocellular carcinoma. In the pancreas GSTP was present in ductal and centroacinar cells, whilst GSTA was present in acinar cells. GSTM was universally present in the cells of islets of Langerhan, not demonstrating genetic polymorphism. In both chronic pancreatitis and pancreatic carcinoma increased expression of GSTP was demonstrated. Using affinity chromatography and high performance liquid chromatography GSTA, P and M were purified from human pancreatic tissue. A novel GST isoenzyme, which ran on SDS/PAGE, similar to GSTP, was identified, purified and confirmed by Western blot analysis to be a GSTA. Feeding rats exclusively on raw soya flour resulted in pancreatic hypertrophy and eventually carcinoma. Serial measurements of GST activity showed only a minor reduction with short term feeding which returned to normal with chronic administration contrary to what has been proposed (Ross & Barrowman, 1987). No selective change in GST isoenzymes was identified. A dominant cytoplasmic protein, shown both enzymatically and by Western blot analysis to be α-amylase fell dramatically with short term administration recovering only marginally with chronic administration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available