Abstract
A cell line (MRc40) resistant to the model quinone compound, menadione, has been isolated from a parental Chinese hamster ovary cell line (CHO-K1). The known relationship between menadione toxicity and glutathione (GSH) depletion led us to investigate whether the mechanism of resistance of MRc40 was related to alteration in GSH homeostasis. Intracellular concentrations of GSH and cysteine (CySH) were twofold and 3.2-fold greater in MRc40 than in CHO-K1. Following exposure to menadione, GSH and CySH were depleted, but subsequent recovery of thiols was more rapid and of greater magnitude in MRc40 than in CHO-K1. Twelve hours after exposure to menadione, the concentrations of GSH and CySH were 9.7- and 4.2-fold greater in MRc40 than in CHO-K1. Using nuclear magnetic resonance (NMR) spectroscopy, we observed the in situ removal of menadione from cell suspensions of CHO-K1 and MRc40. However, only in CHO-K1 did we observe concomitant depletion of NMR-visible GSH. We conclude that the perturbation of GSH metabolism contributes to the resistant phenotype and is an important characteristic of menadione-resistant CHO cells.
Highlights
ObjectivesThe purpose of this study was to investigate alteration in reduced glutathione (GSH) homeostasis in a Chinese hamster ovary (CHO) cell line following acquisition of resistance to menadione
We conclude that the perturbation of reduced glutathione (GSH) metabolism contributes to the resistant phenotype and is an important characteristic of menadione-resistant Chinese hamster ovary (CHO) cells
We have previously reported the isolation of menadione-resistant cell lines that overexpress GSH (Vallis and Wolf, 1996)
Summary
The purpose of this study was to investigate alteration in GSH homeostasis in a Chinese hamster ovary (CHO) cell line following acquisition of resistance to menadione
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