PT  - JOURNAL ARTICLE
AU  - ERNEST F. ZIMMERMAN
AU  - STEPHEN A. GREENBERG
TI  - Inhibition of Protein Synthesis by 8-Azaguanine I. Effects on Polyribosomes in HeLa Cells
AID  - 10.1124/mol.1.2.113
DP  - 1965 Sep 01
TA  - Molecular Pharmacology
PG  - 113--125
VI  - 1
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/1/2/113.short
4100  - http://molpharm.aspetjournals.org/content/1/2/113.full
SO  - Mol Pharmacol1965 Sep 01; 1
AB  - In HeLa monolayer and suspension cultures azaguanine causes a preferential inhibition of protein synthesis; RNA and DNA synthesis are inhibited to a lesser extent and at later times. The effects of azaguanine were explored by measuring protein synthesis on the cytoplasmic polyribosomes that were isolated by sucrose gradient centrifugation. Azaguanine (3 x 10-4 M) after 24 hours pretreatment of HeLa, decreased protein synthesis per unit of polyribosome to 44% of control. The appearance of mRNA in polyribosomes of the drug-treated culture was not impaired. Synthesis of cytoplasmic ribosomes was suppressed by about 50-60%. Azaguanine was incorporated into both mRNA and ribosomal RNA molecules of the polyribosome structure. Azaguanine (3 x 10-4 M) did not inhibit protein synthesis in rabbit reticulocytes even after 20 hours’ exposure to the drug. It was concluded that azaguanine inhibits protein synthesis not by blocking the formation of polyribosomes but rather by incorporation into mRNA of this structure. ACKNOWLEDGMENT This work was supported by a grant (T39) from the American Cancer Society to Dr. Avram Goldstein.