Ascorbate and thiol antioxidants abolish sensitivity of yeast Saccharomyces cerevisiae to disulfiram

Abstract

Sensitivity of baker's yeast to disulfiram (DSF) and hypersensitivity of a mutant devoid of Cu, Zn-superoxide dismutase to this compound is reported, demonstrating that yeast may be a simple convenient eukaryotic model to study the mechanism of DSF toxicity. DSF was found to induce oxidative stress in yeast cells demonstrated by increased superoxide production and decrease of cellular glutathione content. Anoxic atmosphere and hydrophilic antioxidants (ascorbate, glutathione, dithiothreitol, cysteine, and N-acetylcysteine) ameliorated DSF toxicity to yeast indicating that oxidative stress plays a critical role in the cellular action of DSF.