Abstract
The effect of 5-fluorouracil on the synthesis, methylation and its incorporation into low molecular weight nuclear RNA was studied in L1210 cells in vitro. 5-Fluorouracil was incorporated into high molecular weight, 5 S and 4 S nuclear RNA at a linear rate for 2 hr following an initial lag period. Drug concentrations of 1 x 10-5 to 1 x 10-4 M did not have a marked effect on the incorporation of [3H]adenosine into 5 S and 4 S nuclear RNA; however, the synthesis of high molecular weight nuclear RNA was inhibited 10-60% depending on the length of time of labeling and the drug concentration. 5-Fluorouracil impaired the methylation of 4 S nuclear RNA in a dose-dependent manner and affected high molecular weight nuclear RNA to a lesser extent. 5-Fluorouracil at 1 x 10-4 M inhibited the methylation of eight methylated nucleosides in 4 S nuclear RNA, but at 5 x 10-5 M preferentially affected 7-methylguanosine, N2, N2-dimethylguanosine and 5-methyluridine. These results indicate that the methylation of 4 S nuclear RNA is impaired by 5-fluorouracil at concentrations of drug which do not significantly impair its transcription.
ACKNOWLEDGMENT The authors wish to thank Mrs. Margaret Green for help in the preparation of this manuscript.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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