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Title: Menadione resistance : a model for cellular defences against oxidative stress
Author: Vallis, Katherine Anne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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To study the genetic changes which confer resistance to oxidants, cell lines that are resistant to the redox-cycling agent, menadione, have been isolated from Chinese hamster ovary (CHO) and human transitional carcinoma (EJ) parental cell lines. They exhibit cross-resistance to chemical oxidants (hydrogen peroxide and sodium arsenite) but not to ionising radiation (in oxic conditions). The concentrations of the major sources of intracellular thiol groups, glutathione and cysteine, are two-fold greater in menadione-resistant than in the corresponding parental cell lines. Exposure to menadione results in depletion of both glutathione and cysteine but the subsequent recovery of thiols is more rapid and of greater magnitude in menadione-resistant than sensitive cell lines. 1H spin echo nuclear magnetic resonance (NMR) spectroscopy was used to study intact cells. Using this technique the removal of menadione from suspensions of resistant and sensitive cells was observed. However, only in menadione-sensitive cells was concomitant depletion of the NMR-visible pool of glutathione observed. The acquisition of resistance to menadione was associated with significant changes in the expression of several enzymes that are implicated in the oxygen-induced stress response and in protection from redox-cycling agents. The transcription of genes encoding heme oxygenase and the glutathione-related enzymes, GST-Pi and glutathione peroxidase, increases in CHO parental cells after transient oxidative stress. These genes are constitutively induced in CHO menadione-resistant cell lines. This suggests that resistance results from perpetuation of a response that normally occurs only transiently.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available