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