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 H2O 2 challenge. In contrast, cells that have been preexposed to relativel y low H2O2 priming treatments (i.e., cells that have first been pretre ated with low H2O2 concentrations) are able to survive a subsequent ch allenge dose and continue to divide at normal rates. The most effectiv e adaptation was observed with the following conditions: 5 X 10(6) cel ls/ml at pretreatment, pretreatment or priming peroxide addition of 0. 4 mM H2O2, interval between pretreatment and challenge of 45 min, chal lenge peroxide concentration of 0.8 mM H2O2 for 2 h. Under these condi tions cells that were challenged without pretreatment exhibited a 90% loss of plating efficiency. In contrast, peroxide-pretreated cells gre w and divided at rates that were actually 15-30% faster than those of nonpretreated cells, and some 90-100% of such pretreated cells continu ed to divide at normal rates even following exposure to the H2O2 chall enge concentration. The increased H2O2 resistance of pretreated cells was transient, being readily reversed during 60-90 min of growth in th e absence of H2O2. Furthermore, cells that were allowed to deadapt ove r a 4 h period again exhibited a transient adaptive response when reex posed to H2O2 pretreatment. These results, plus the high survival rate s (90-100%) of H2O2 pretreated and challenged cells, demonstrates that our results represent a true transient adaptation, rather than a sele ction for any preexisting peroxide resistant subpopulation. H2O2 adapt ation required protein synthesis as evidenced by studies with the tran slational inhibitor, cycloheximide. At least 21 proteins exhibited inc reased expression following H2O2 adaptation, while the expression of s ome 8 other proteins was decreased. Adaptation is now widely reported in bacterial strains and has also been observed in some mammalian cell lines. Tire propose that the basis for such adaptive responses rests in increased expression of genes that encode protective enzymes and re pair enzymes. (C) 1995 Academic Press, Inc.