Molecular Pharmacology, Vol 2, 534-542, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Protein and RNA Synthesis in HeLa Cells by Levallorphan and Levorphanol

¹ McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

The effects of levallorphan, N-allyl-3-hydroxymorphinan, on biosynthetic functions of intact HeLa cells and subcellular fractions were examined. When cell cultures were treated in vivo with the agent, DNA and lipid synthesis were unaffected; the incorporation of guanine into ribosomal, rapidly labeling, and soluble RNA was reduced; and the RNA polymerase activity of isolated nuclei was depressed. The inhibitory action on RNA synthetic functions seemed to result from a reduction in the protein synthesizing capacity of the cell, which was correlated with dissociation of the polysomes and a reduced ability of subcellular fractions from treated cells to support the incorporation of amino acids. When added directly, levallorphan did not inhibit the synthesis of protein and RNA by in vitro systems. The data presented support the conclusions that the primary effect of levallorphan is the inhibition of protein synthesis, brought about by interference with the utilization of messenger RNA. The results confirm the strong dependence of RNA synthesis in HeLa cells on synthesis of protein.

Note:
ACKNOWLEDGMENTS The authors wish to express their gratitude to Dr. W. E. Scott and Hoffmann-La Roche, Inc. for generous gifts of levallorphan and levorphanol tartrate. This investigation was supported by U. S. Public Health Service Grant CA-07175 from the National Cancer Institute.