Molecular Pharmacology, Vol 16, 270-277, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of 5-Fluorouracil on the Synthesis of Nuclear RNA in L1210 Cells In Vitro

¹ Applied Pharmacology Section, Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20014

The effect of 5-fluorouracil on nuclear RNA synthesis and its incorporation into nuclear RNA were studied in L1210 cells in vitro. Inhibition of the incorporation of [³H]uridine into total RNA by 5-fluorouracil was proportional to the incorporation of drug into RNA. The antimetabolite inhibited the labeling of total nuclear RNA by [³H]uridine but not its methylation. Fractionation of nuclear RNA into ribosomal RNA, nonpolyadenylic acid-heterogeneous RNA and polyadenylic acid-heterogeneous RNA revealed that although incorporation of [³H]uridine was impaired by 5-fluorouracil, the incorporation of [³H]-adenosine was not; however, polyadenylic acid synthesis was significantly impaired by 5-fluorouracil. The incorporation of [³H]5-fluorouracil into the three species of nuclear RNA revealed that the concentration of drug per unit of RNA was greatest in polyadenylic acid-heterogeneous RNA, while the non-poly(A)heterogeneous RNA fraction contained the greatest total amount of 5-fluorouracil. These results show that although transcription is not impaired by 5-fluorouracil, posttranscriptional polyadenylation is inhibited. Moreover, incorporation of 5-fluorouracil into nuclear RNA, and particularly polyadenylic acid-containing RNA, appears to be the predominant feature of this drug with respect to transcription in L1210 cells.

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ACKNOWLEDGMENT The authors would like to thank Mrs. Margaret Green for typing the manuscript.