Abstract
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.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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