The use of Saccharomyces cerevisiae as a model system to study the mechanism of action of chemical antioxidants

Abstract

Butylated hydroxyanisole (BHA) is a synthetic substance commonly used as dietary antioxidant which plays an important role in protecting foods from oxidation. It has been reported that this compound caused an increase in glutathione-s-transferase specific activity, which is responsible for resistance to oxidative stress, i.e., there was some evidence that it could act as a pro-oxidant. In the present study, BHA was found to be toxic towards yeast and this was investigated further by determining its effect on the viability of a variety of yeast mutants lacking key genes required for resistance to oxidative stress. The results showed that the cell viability of the mutants was not significantly different from the wild type parental strains. This suggests that BHA toxicity was unlikely to involve reactive oxygen species (O2 - and H2O2) and might not directly involve the classical oxidant stress responses found in yeast cells. Interestingly, the pre-treatment of yeast cells with low concentrations of BHA (0.2 mM) and subsequent exposure to higher concentrations of either BHA or hydrogen peroxide (H2O2) resulted in pre-treated yeast cells becoming more resistant to both toxic levels of BHA and H2O2 than non pre-treated cells. These findings indicated that low level of BHA could induce an adaptive response to BHA and induce cross-protection against H2O2. A genetic approach was adopted to identify genes involved in this process, involving the isolation and characterisation of BHA sensitive mutants. The results demonstrated that the yeast genes TYR1, KRE6 and GPH1 play role in the cells response towards BHA.