Effect of cycloheximide on protein biosynthesis in rat liver.

1. The liver ribosomes of rats given cycloheximide by intraperitoneal injection incorporate less amino acid into protein than ribosomes from control rat liver when they are incubated in vitro with excess of Sephadex-treated cell sap. The effect is rapid, marked and persistent. 2. Cell sap from liver of cycloheximide-treated animals is inhibitory but the inhibition can be relieved almost entirely by treating the cell sap with Sephadex. No damage has been done to the cell-sap factors: it is suggested that the dissolved cycloheximide in the cell sap causes the inhibition. 3. Cycloheximide added in vitro inhibits amino acid incorporation into protein in the presence or absence of polyuridylic acid. The inhibition is lessened by addition of excess of cell sap but is not abolished. 4. The differences between these results and those obtained with mouse liver (Trakatellis, Montjar & Axelrod, 1965) might arise because of species differences in sensitivity to the drug.