In Candida albicans the continued increase in dry weight, in cell volume and in hyphal length during 5FC treatment is mainly due to increased amount of carbohydrate despite the decreased amounts of nucleic acids. Incorporation studies with 32PO4 (for RNA) in C. albicans and with 3H-thymidine-monophosphate (for DNA) in a thymidine-utilising strain of Saccharomyces cerevisiae have shown that the decreased amounts of nucleic acids were due to an inhibition of synthesis of RNA and DNA by 5FC. Nuclear-staining techniques on the hyphal phase of C. albicans showed that 5FC inhibits nuclear division. The changes in amounts of protein during 5FC treatment do not wholly explain the changes in cell size although 14C-histidine incorporation experiments showed that protein synthesis continued in the presence of 5FC. 14C-glucose incorporation in the presence of 5FC showed an initial accelerated synthesis of carbohydrate with a maintained level of synthesis after 16 h. This abnormal pattern of synthesis correlates with the increase in amount of carbohydrate and in cell size and hyphal elongation. 5FC inhibits DNA synthesis, and all manifestations of unbalanced growth that culminate in the cell volume changes appear to be a consequence of that inhibition.
AraiT.,
MikamiT.,
YokoyamaK.,
KawataT.,
MasudaK.1977Morphological changes in yeasts as a result of the action of 5-fluorocytosine. Antimicrob. Agents Chemother. 12:255
CohenS. S.,
FlaksJ. G.,
BarnerH. D.,
LoedM. R.,
LichtensteinJ.1958; Themodeof action of 5-fluorouracil and its derivatives. Proc. natn. Acad. Sci. U. S. A 44:1004
GiegeR.,
WeilJ. H.1970; Etudes des t-RNA de levure ayant incorpore du 5-fluorouracil provenant de la deamination in vivo de la 5-fluorocytosine. Bull. Soc. Chim. biol 52:135
PolakA.,
WainW. H.1977; The influence of 5-fluorocytosine on nucleic acid synthesis in C. albicans, Cr. neoformans and A. fumigatus. Chemotherapy 23:243
ScholerH. J.,
PolakA.1973; Fungistatic and fungicidal properties of 5-fluorocytosine; methods for routine sensitivity tests. Symposium International de Mycologie Medicale Bucarest: p 37
TrevelyanW. E.,
HarrisonJ. S.1956; Studies on yeast metabolism. 7. Yeast carbohydrate fractions. Separation from nucleic acid, analysis, and behaviour during anaerobic fermentation. Biochem, J 63:23
WainW. H.,
PriceM. F.,
BraytonA. R.,
CawsonR. A.1976a; Macromolecular syntheses during the cell cycles of yeast and hyphal phases of Candida albicans. J. gen. Microbiol 97:211