5-Fluoro-orotic acid induces chromosome alterations in Candida albicans

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.