Yeast mitochondrial deoxyribonuclease stimulated by ethidium bromide. III. Possible invovlement in the induction of "petite" mutation by phenanthridinium derivatives.

We previously described a yeast-mitochondrial deoxyribonuclease (EtdBr DNAase), whose activity is stimulated by ethidium bromide. In this paper, we have compared the ability of a series of phenanthridinium derivatives to activate the EtdBr DNAase "in vitro" and their efficiency in inducing "petite" mutants in the yeast S. cerevisiae. Kinetics studies, in the absence or the presence of SDS, were first carried out to compare the penetration rates of the various compounds. Dose--response curves were then established to quantify their mutagenic efficiencies. From these data, a linear correlation was established between the level of EtdBr DNAase activation produced by a drug and its mutagenic efficiency, thus demonstrating that the two processes display similar drug-structural requirements. These results suggest that the EtdBr DNAase might be involved in the induction of petite mutations by these derivatives.