RT Journal Article
SR Electronic
T1 The Effect of 5-Fluorouracil on the Synthesis of Nuclear RNA in L1210 Cells In Vitro
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 270
OP 277
VO 16
IS 1
A1 ROBERT I. GLAZER
A1 ANN L. PEALE
YR 1979
UL http://molpharm.aspetjournals.org/content/16/1/270.abstract
AB 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. ACKNOWLEDGMENT The authors would like to thank Mrs. Margaret Green for typing the manuscript.