title: 5-Fluoro-orotic acid induces chromosome alterations in Candida albicans.
abstract: Treatment of a prototrophic laboratory strain of Candida albicans with 5-fluoro-orotic acid (5-FOA) produced two major types of mutants with chromosomal alterations, 5-FOA-resistant (FoaR) and those remaining sensitive (FoaS). Both major types remained Ura+. FoaR mutants, produced after a long exposure, contained either a duplication of chromosome 4b or an inner enlargement of chromosome 5b. The average mutant frequency was approximately 1.0 x 10(-5). The reverse mutation of FoaR to FoaS also caused the loss of either the extra chromosome 4b or the enlarged chromosome 5b, revealing a causal relationship between the resistance and the specific chromosome constitution. The cells remained sensitive after a relatively short 24 h exposure to 5-FOA medium, but the treatment induced non-specific changes in lengths of various chromosomes. Furthermore, FoaR type mutants acquired a notable chromosomal and phenotypic instability. Our results indicate the necessity of electrokaryotyping of strains that have been exposed to 5-FOA, especially with studies of gene function and with DNA microarray assays.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wellington
authors.forename: Elena
authors.initials: E
authors.lastname: Rustchenko
mesh_terms: D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D002869:Chromosome Aberrations; D015825:Chromosomes, Fungal / Q000187:drug effects*; D007621:Karyotyping; D009154:Mutation; D009963:Orotic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010641:Phenotype
chemical_list: D009963:Orotic Acid; C001242:5-fluoroorotic acid