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.