5-Fluorocytosine (5-FC) has a rapid inhibitory effect on the synthesis of RNA and DNA in the yeast and hyphal form of Candida albicans. 5-FC has a less marked effect on the RNA and DNA content of sensitive strains of Cryptococcus neoformans and has no effect on the nucleic acid content of Aspergillus fumigatus nor of resistant strains of C. albicans and C. neoformans. 5-FC has a slower inhibitory effect on yeast cell number increase and no effect on hyphal length of hyphal phase C. albicans over a 7-h incubation period. Rapidly growing yeasts of C. albicans and C. neoformans decrease in volume and in dry weight per cell. 5-FC prevents this decrease in sensitive strains. These results have been discussed with respect to the known metabolic pathway of 5-FC, the fungistat-ic and fungicidal action of 5-FC and the development of resistance to 5-FC.

SUMMARYSynchronous cultures of yeast and hyphal phases of Candida albicans showed exponential increases in RNA content and stepwise exponential increases in DNA content. The periods of DNA synthesis in the two phases coincided with one another and with the budding peaks of the yeast phase. Hyphae grown in synchronous cultures also showed an exponential increase in length. The hyphal phase was therefore normal.Hyphal nuclear division occurred after hyphal DNA synthesis, Germination was a unique event for a hypha and unlike yeast bud formation, preceded the first period of DNA synthesis.The exponential increase in RNA and DNA in asynchronous cultures of hyphae in serum paralleled the exponential increase in the numbers of cells in asynchronous cultures of yeasts in defined media. Thus there are no factors in serum which inhibit the normal exponential growth of C. albicans,

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5-FLUOROCYTOSINE (5FC) has an important place in the treatment of systemic mycoses in man. Its mode of action was initially explained by an extensive incorporation of the deaminated form, 5-fluorouracil, into fungal RNA, with this leading to a disturbance of the internal amino-acid pool (Polak, 1974). Recently, the inhibition of RNA and DNA syntheses has been reported by Polak and Wain, (1977; and by Diasio, Bennett and Myers (1978). The inhibition of DNA synthesis in Escherichia coli by trimethoprim or by 5-fluorodeoxyuridine is rapidly bactericidal (Cohen et al., 1958 ;Angehrn and Then, 1973) but there is no evidence of 5FC having a rapid fungicidal action on Candida albicans (Scholer and Polak, 1973).Primary resistance to 5FC has been reported by Speller and Davies (1973) and is considered to involve several mechanisms in the pathway of RNA synthesis (Polak and Scholer, 1975), which mechanisms may also affect DNA synthesis. The dimorphism of C. albicans affects the development of resistance to 5FC (Davies and Savage, 1974) and the hyphal form may be associated with the invasive ability of this opportunist fungus (Montes and Wilborn, 1968 ;Cawson and Rajasingham, 1972; Wain, Price and Cawson, 1976~).Because the inhibition of DNA synthesis by 5FC was accompanied by an increase in blastospore cell volume and hyphal length, the effect of the drug on the protein and carbohydrate metabolism of the fungus in its hyphal and blastospore forms has been investigated and studies with radioactive precursors have been undertaken to elucidate the inhibition of DNA and RNA syntheses. MATERIALS AND METHODS Microorganisms

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