Evaluation of the genotoxic spectrum of cisplatin for Candida albicans

Abstract

The platinum co-ordination complex cisplatin [cis-diamminedichloroplatinum (II)] is a highly effective anticancer drug whose activity derives from its ability to form adducts crosslinking neighbouring purine bases in DNA. Under in vitro conditions, cisplatin induced cellular inactivation, forward and reverse mutations, reciprocal and nonreciprocal mitotic recombinations and phenotypic switching in the opportunistically pathogenic yeast Candida albicans. Mutant and recombinant yields were higher with post-treatment growth at 25 degrees C rather than 37 degrees C: the reverse was true for cell death or phenotypic switches. These responses comport with prior evidence that, generally, the higher recovery temperature discourages DNA repair processes in C. albicans. Thiosulphate, an agent used therapeutically to reduce nephrotoxic side effects of cisplatin in humans, greatly decreased both the lethality and recombinagenicity of cisplatin for C. albicans. Implications of these observations for possible genetic destabilization of C. albicans populations born naturally by cancer patients undergoing treatments with cisplatin are discussed.