Cytostatic, cytotoxic and mutagenic effects of voacristine, an indole alkaloid in wild-type and repair-deficient yeasts

Voacristine, an indole alkaloid isolated from the leaves of Ervatamia coronaria (Stapf.) (Apocynaceae) has dose-dependent cytostatic and cytotoxic effects on cultures of Saccharomyces cerevisiae. These inhibitory effects take place only in growing cells. Among the different repair-deficient mutants examined, a mutant defective in excision-resynthesis repair pathway (rad3-e5) was found to be the most sensitive to such a toxic effect. The mutant rad52-1 blocked in the DNA strand break repair pathway showed an intermediary sensitivity to the lethal effect induced by this indole alkaloid, whereas the mutant defective in the mutagenic repair pathway (rad6-1) demonstrated practically the same sensitivity as the wild-type strain. The nuclear reversion mutation for the locus lysl-1 was induced by voacristine, whereas the mitochondrial "petite" mutation was not induced by this alkaloid. These results indicate that the lesions induced by voacristine in vivo are likely to be of the adducts type; such damage is repairable in the wild-type; the DNA strand break repair pathway plays a minor role in the repair of voacristine-induced lesions.