Inhibition of Ribosomal Ribonucleic Acid Maturation in Novikoff Hepatoma Cells by 5-Fluorouracil and 5-Fluorouridine

Abstract 5-Fluorouracil, at 10-4 m concentrations, inhibited ribosomal RNA maturation only slightly in Novikoff hepatoma cells growing in suspension culture. On a molar basis, 5-fluorouridine was a much more potent inhibitor of the maturation process. The difference between the effectiveness of 5-fluorouracil and 5-fluorouridine is probably a result of the greater transport and incorporation of the latter into RNA. The nucleoside analogue strongly inhibited the production of mature 18 S and 28 S ribosomal RNA, while apparently only slightly inhibiting the formation of the initial 45 S ribosomal precursor RNA or the 38 S ribosomal RNA intermediate. Inhibition of 32 S ribosomal precursor RNA production was greater than that of the larger precursor molecules, but less than that of the mature ribosomal RNA molecules. 5-Fluorouridine did not affect the methylation of 45 S ribosomal precursor RNA, indicating that the analogue exerts its inhibitory effect on some other aspect of the ribosomal RNA maturation process.