Molecular Pharmacology, Vol 3, 124-132, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Effects of -Phenethyl Alcohol on Mouse L Cells in Suspension Culture

I. Reversible Inhibition of Cell Proliferation and Effects on the Uptake of Labeled Precursors of Nucleic Acid and Protein

¹ Department of Medical Biophysics, University of Toronto, and The Ontario Cancer Institute, Toronto, Ontario, Canada

-Phenethyl alcohol (PEA) was found to be an effective inhibitor of the proliferation of mouse L cells in suspension culture. Both its action as an inhibitor and its toxicity were found to be critically dependent on concentration and duration of exposure. The inhibition of proliferation caused by exposure of cells to 0.10% PEA (8.2 x 10^-3 M) was almost fully reversible even after periods of exposure to PEA as long as 12 days. This concentration of PEA caused a rapid decrease in the uptake of labeled precursors of DNA, RNA, and protein into mouse L cells. For each precursor, the initial reduction in uptake was complete within 20 minutes after the addition of PEA. Following this drop, there was a residual low level of DNA synthesis, as measured by thymidine-³H incorporation, which depended on the concentration of PEA used. The rate of DNA synthesis remained depressed over the next 5 days in the presence of PEA. The sudden initial depression of uridine-¹⁴C and leucine-¹⁴C uptake in PEA-treated cells was accompanied by a rapid reduction in the number of cytoplasmic polyribosomes with a concomitant increase in the number of single ribosomes. In the continuing presence of PEA, the depression of uridine-¹⁴C and leucine-¹⁴C uptake was succeeded by a transient recovery to higher levels of incorporation, reaching a maximum about 10 hours after the addition of PEA.

These results indicate that PEA is not a specific inhibitor of DNA synthesis in mammalian cells.

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ACKNOWLEDGMENTS This work was supported in part by grants from the National Cancer Institute of Canada, and the USPHS (Grant CA-06229-04). The authors are grateful to Mr. S. Gulyas for his assistance.