Action on ricin and its polypeptide chains on cultured hepatoma cells

The effect of ricin, the glycoproteic toxin from castor beans, as well as of its two polypeptide chains A and B, was studied on hepatoma tissue cell suspension cultures (HCT). The isolated A and B chains have no action. Ricin at a 0.3 microgram/ml concentration, for 3 x 10(5) cells/ml, has a cytostatic effect which becomes cytotoxic after 72 h. This effect exists even if the cells are preincubated for 4 with ricin and washed afterwards. The protein content of the ricin-treated cells decreases. Protein synthesis measured by the incorporation of [3H]-leucine in the cell proteins begins to be inhibited after 30 min and is completely blocked after 2 h for a ricin concentration of 0.3 microgram/ml. DNA synthesis is inhibited from 1 h on. Finally the level of the DNA slows down from 3 h on, whereas the level of RNA abruptly falls between 4 and 5 h. The inhibitory effects are likely to be a consequence of protein synthesis inhibition, but a direct effect on the nucleic acids is not excluded.