Transient adaptation to oxidative stress in yeast.

Adaptive responses to the oxidative stress of hydrogen peroxide (H2O2) were studied in the yeast Saccharomyces cerevisciae strain RZ53. Our results show that the growth of naive cells is readily arrested by H2O2 challenge. In contrast, cells that have been preexposed to relatively low H2O2 priming treatments (i.e., cells that have first been pretreated with low H2O2 concentrations) are able to survive a subsequent challenge dose and continue to divide at normal rates. The most effective adaptation was observed with the following conditions: 5 x 10(6) cells/ml at pretreatment, pretreatment or priming peroxide addition of 0.4 mM H2O2, interval between pretreatment and challenge of 45 min, challenge peroxide concentration of 0.8 mM H2O2 for 2 h. Under these conditions cells that were challenged without pretreatment exhibited a 90% loss of plating efficiency. In contrast, peroxide-pretreated cells grew and divided at rates that were actually 15-30% faster than those of nonpretreated cells, and some 90-100% of such pretreated cells continued to divide at normal rates even following exposure to the H2O2 challenge concentration. The increased H2O2 resistance of pretreated cells was transient, being readily reversed during 60-90 min of growth in the absence of H2O2. Furthermore, cells that were allowed to deadapt over a 4-h period again exhibited a transient adaptive response when reexposed to H2O2 pretreatment. These results, plus the high survival rates (90-100%) of H2O2 pretreated and challenged cells, demonstrates that our results represent a true transient adaptation, rather than a selection for any preexisting peroxide resistant subpopulation. H2O2 adaptation required protein synthesis as evidenced by studies with the translational inhibitor, cycloheximide. At least 21 proteins exhibited increased expression following H2O2 adaptation, while the expression of some 8 other proteins was decreased. Adaptation is now widely reported in bacterial strains and has also been observed in some mammalian cell lines. We propose that the basis for such adaptive responses rests in increased expression of genes that encode protective enzymes and repair enzymes.