Molecular Pharmacology, Vol 2, 50-55, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Inhibitory Effects of Acetoxycycloheximide, Puromycin, and Pactamycin upon Synthesis of Protein and DNA in Asynchronous Populations of HeLa Cells

¹ Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, New York

The rate of incorporation of thymidine into DNA of HeLa cells decreased within 10 min following exposure of these cells to an adequate concentration of acetoxycycloheximide, puromycin, or pactamycin. While uptake of leucine was inhibited in excess of 95% by these drugs, inhibition of incorporation of thymidine did not exceed 70% within the first hour. Incorporation of uridine into RNA was unaffected by acetoxycycloheximide but was decreased by high concentrations of puromycin and pactamycin. Concentration-effect and temporal relationships of these drug-induced phenomena indicate that interruption of protein synthesis is a primary effect; impairment of synthesis of DNA is a secondary event resulting from the disturbance in protein metabolism. Inhibition of precursor incorporation into RNA by high levels of puromycin and pactamycin seems unrelated to the action of these drugs on the biosynthesis of proteins. These results suggest the existence of a close temporal coupling between the synthesis of a protein species and the replication of DNA in an asynchronous population of mammalian cells in exponential growth.

Note:
ACKNOWLEDGMENT The author is grateful to Dr. B. K. Bhuyan for making his observations on pactamycin available prior to their formal publication. This work has been supported in part by Public Health Service Research Grant CA-07860 from the National Cancer Institute.

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