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Title: Regulation of glutathione S-transferases during stress
Author: Hill, Alison Elspeth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Elevation of glutathione S-transferases (GST) in tumour cells can be responsible for resistance to a variety of chemotherapeutic agents. It has been hypothesised that GSTs may be induced as part of a stress response, similar to that of the prokaryotic adaptive response. To further this investigation I studied the induction of GSTs in a variety of permanent and transient stress models. A chlorambucil resistant CHO cell line which was known to express increased levels of Alpha-class GST was studied to determine the nature of the increase in protein. Northern and Southern blot analysis revealed a 4-8 fold amplification in the DNA encoding the Alpha-class GSTs with an accompanying increase in mRNA levels. Elevated levels of an Alpha-class GST were noted in oxygen resistant CHO cells. Transient exposure to 98% oxygen also induced the same Alpha-class GST. A heat shocked lung tumour cell line as well as heat selected sublines showed some changes in the levels of Pi- and Mu-class GSTs. A novel putative Mu-class GST subunit has been identified in the nucleus of heat shocked cells. The nature of the GST level variations at the RNA and DNA levels were studied. These studies do not suggest co-ordinate regulation of the GSTs as part of a general stress response. It does not exclude the possibility of GST π and perhaps the nuclear Mu-class GST are induced as part of a more limited response either to heat or in certain tissues. Inconsistencies in the data from the preliminary induction experiments led to the investigation of the effect of growth conditions on GST levels. Unexpectedly isoenzymes from three classes of GST were found to be elevated by increased confluence and a low frequency of feeding. This response was found to be mediated through the culture media.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available