Genetic destabilization of Candida albicans by hydroxyurea

Abstract

Candida albicans is a commensal component of the normal human microflora, but frequently causes infections in persons undergoing treatment for malignancies. The cytotoxicity and genotoxicity of the antineoplastic agent hydroxyurea (HU) for the yeast is demonstrated. Cultivation of the organism on defined complete medium in the presence of HU induced growth inhibition or cell death, gene mutations, segregations of heterozygous loci through reciprocal and nonreciprocal mitotic recombinations, and a special heritable system for high frequency switching between phenotypes reflecting cellular growth characteristics and susceptibilities to HU. Each of these responses is influenced differently by variations in drug concentration and temperature. The biochemical complexity underlying cytotoxic and genetic effects of HU, and the implications for the likelihood of HU induced changes occurring in indigenous yeast populations of persons undergoing therapy with the drug, are discussed.