The induction of mutation in yeast by hydrogen peroxide.

The inactivation and mutation to respiratory deficiency of yeast cells by H2O2 are shown to vary progressively with the phase of cell growth, with a sharp transition occurring as the cells complete logarithmic growth. Respiratory deficient mutants isolated from the wild-type population are of two types, one of which is much more sensitive to H2O2 but forms only a small fraction of the mutant sub-population. Based upon the response of the more resistant type, mutation frequency increases appear to result from selection of pre-existing mutants in log phase populations, while induction occurs in stationary phase cells. The induced mutation frequency fits a (dose)2 relationship, but the frequency is depressed when the dose is high (or number of cells treated is low). All the induced mutants are extranuclear and of the resistant type, and show a wide range of suppressiveness in crosses to respiratory competent cells. This may indicate mitochondrial DNA is altered to different extents by H2O2; by the same criterion, the spontaneously occurring H2O2 -sensitive mutants retain a large amount of mitochondrial DNA information, in agreement with their colonial morphology. A small increase in forward mutation of nuclear genes was also found after H2O2 treatment. Parallels are drawn between the response of yeast cells to ionising radiation and to H2O2, and it is suggested that radical action may be involved in inactivation and mitochondrial genome mutation induced by both agents.