The effect of 5-fluorocytosine on the synthesis of 80S ribosomes by pathogenic fungi.
We studied the influence of 5-fluorocytosine(5FC) on the monomeric 80S ribosomes isolated by gradient ultracentrifugation from Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Wangiella dermatitidis. Labelling of the cultures with 32PO4 and [3H]-leucine showed marked inhibition of both ribosomal RNA and ribosomal protein synthesized during the contact of the fungi with the drug. The degree of inhibition was very similar for the synthesis of both ribosomal constituents, (mostly 60-80% each during the initial hours of the contact). This indicates that some ribosomes were still synthesized in the presence of 5FC and that the drug inhibits the synthesis of complete ribosomes to the same extent as the synthesis of ribosomal RNA and protein. By labelling fungi with [14C]-5FC it was shown that in those 80S ribosomes that were still synthesized, large quantities of the drug were incorporated--doubtless as 5-fluorouracil (5FU) in RNA. It can be concluded that RNA containing 5FU is still capable of combining with protein to form complete ribosomes of normal conformation. This is, however, no proof that these ribosomes would have a normal function.
D002474:Cell-Free System; D003596:Cytosine / Q000031:analogs & derivatives*; D005437:Flucytosine / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis; D005658:Fungi / Q000187:drug effects* / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000096:biosynthesis; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity
D005656:Fungal Proteins; D012331:RNA, Fungal; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D003596:Cytosine; D005437:Flucytosine