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Research ArticleArticle

The Comparative Effects of 5-Azacytidine and Dihydro-5-azacytidine on Polysomal RNA in Ehrlich Ascites Cells in Vitro

HSIN-LI LIN and ROBERT I. GLAZER
Molecular Pharmacology November 1981, 20 (3) 644-648;
HSIN-LI LIN
Applied Pharmacology Section, Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20205
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ROBERT I. GLAZER
Applied Pharmacology Section, Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20205
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Abstract

The comparative effects of 5-azacytidine (AZC) and dihydro-5-azacytidine (DHAZC) on the synthesis of polysomal RNA, as well as the translational activity of drug-modified poly(A)RNA were studied in Ehrlich ascites cells in vitro. AZC inhibited the incorporation of [3H]adenosine into non-poly(A)RNA in a concentration-dependent manner, but did not affect the synthesis of poly(A)RNA. In contrast, neither RNA fraction was significantly affected by equimolar concentrations of DHAZC except at 10-3 M, where 40% inhibition of the synthesis of only non-poly(A)RNA was achieved. Electrophoretic characterization of non-poly(A)RNA revealed that the synthesis of 28 S rRNA was inhibited to a greater extent than was 18 S rRNA by 10-5 M AZC, but to equal extents at 10-4 M drug. Significant inhibition of 28 S and 18 S rRNA occurred only with 10-3 M DHAZC, where approximately 50% inhibition of both rRNA species occurred. Both cytidine analogues were ineffective in inhibiting tRNA synthesis. AZC and DHAZC were incorporated into all species of polysomal RNA, but the amount of drug substitution into a particular species of RNA was not proportional to its effect on the synthesis or function of that RNA. There was more analogue incorporated into poly(A)RNA than into nonpoly(A)RNA, but drug-substituted poly(A)RNA showed neither an impairment of its coding efficiency nor qualitative changes in the translation products synthesized in a rabbit reticulocyte translation system in vitro. From these results, it appears that the relative differences in the inhibitory effects by the two cytidine analogues on rRNA synthesis, as well as their incorporation into rRNA, correlate closely with their relative potencies as antitumor agents.

  • Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics

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Molecular Pharmacology
Vol. 20, Issue 3
1 Nov 1981
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Research ArticleArticle

The Comparative Effects of 5-Azacytidine and Dihydro-5-azacytidine on Polysomal RNA in Ehrlich Ascites Cells in Vitro

HSIN-LI LIN and ROBERT I. GLAZER
Molecular Pharmacology November 1, 1981, 20 (3) 644-648;

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Research ArticleArticle

The Comparative Effects of 5-Azacytidine and Dihydro-5-azacytidine on Polysomal RNA in Ehrlich Ascites Cells in Vitro

HSIN-LI LIN and ROBERT I. GLAZER
Molecular Pharmacology November 1, 1981, 20 (3) 644-648;
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