Phenethyl alcohol: Reversible inhibition of synthesis of macromolecules and disaggregation of polysomes in rat hepatoma cells

Abstract

1. The effect of phenethyl alcohol (4–24 mM) on cell division, permeability and cell volume of exponentially growing Novikoff rat hepatoma cells and on their synthesis of macromolecules and membranes was investigated. 2. Phenethyl alcohol inhibits immediately and to about the same extent the synthesis of RNA, DNA and protein, and causes a rapid disaggregation of the polysomes and a marked decrease in nucleosidetriphosphate: RNA nucleotidyltransferase (EC 2. 7. 7. 6) activity of the cells. Cell division is inhibited to a lesser extent than the synthesis of macromolecules which leads to a decrease in the average size of the cells after addition of phenethyl alcohol. Phenethyl alcohol inhibits the incorporation of [ Me- 3H]choline into phosphorylcholine but has little effect on the incorporation of the latter into phosphatidylcholine of mitochondria and cellular membranes. The cells do not become permeable to cytoplasmic proteins or RNA or phosphorylcholine as a result of treatment with phenethyl alcohol. 3. The degree of inhibition of the various cellular processes is directly related to the concentration of phenethyl alcohol employed. The effects are readily reversed by removal of the chemical. The rate of synthesis of protein commences to increase immediately after reversal and this is accompanied by the re-formation of the polysomes. The re-formation of polysomes is largely unaffected by the presence of actinomycin D indicating that messenger RNA persists intact throughout the period of treatment with phenethyl alcohol. The rates of synthesis of RNA and DNA increase more slowly after reversal and cell division is delayed for several hours. 4. The overall results suggest that phenethyl alcohol affects a basic site or process associated with growth control of the cell. Most of the morphological and biochemical changes observed after treatment of cells with phenethyl alcohol resemble those observed during the normal transition of cells from the exponential to the stationary phase of growth.