Molecular Pharmacology, Vol 19, 117-121, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Analysis of the Effect of 5-Fluorouracil on the Synthesis and Translation of Polysomal Poly(A)RNA from Ehrlich Ascites Cells

¹ Applied Pharmacology Section, Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20205

The effects of 5-fluorouracil on the synthesis and translation in vitro of polyadenylic acid-containing polysomal RNA [poly(A)RNA] were studied in Ehrlich ascites cells incubated in vitro. Exposure of cells for 2 hr to concentrations of 5 x 10^-6-5 x 10^-4 M 5-fluorouracil did not significantly alter the size distribution of poly(A)RNA labeled with either [³H]adenosine or [³H]5-fluorouracil. Incorporation of [³H]adenosine into poly(A)RNA was reduced by 28% and 57% at concentrations of 5 x 10^-5 M and 5 x 10^-4 M 5-fluorouracil, respectively. The latter effect correlated with increased drug substitution which ranged from approximately 0.1% to 2% at concentrations of 5 x 10^-6-5 x 10^-4 M 5-fluorouracil. Translation of 5-fluorouracil-substituted poly(A)RNA in vitro in either a rabbit reticulocyte lysate or wheat germ extract system did not indicate a quantitative alteration in messenger RNA activity. Autoradiography of labeled translation products did not indicate major qualitative alterations between control and 5-fluorouracil-modified poly(A)RNA. These results suggest that impairment in the synthesis of messenger RNA occurs only at high concentrations of 5-fluorouracil, but that the integrity of the translational activity of the RNA is not significantly impaired.