Inhibition of tumor cell proliferation by dimerized ribonuclease.

A cross-linked dimer of pancreatic ribonuclease A (ribonucleate 3'-pyrimidino-olitonucleotidohydrolase, EC 3.1.4.22), at a 10 mg/liter concentration, blocks proliferation of tumor cells. The protein retains this ability after inactivation by iodoacetate. The cytostatic effect of ribonuclease preparations on various cell lines correlates well with their rate of uptake: for example, monomeric ribonuclease A is much less effective and is taken up into the cells 10 t0 15 times more slowly. Cell fractionation studies on hepatoma cells indicate accumulation of the dimer in the lysosomal system. Ribonuclease dimer induces a labilization of the lysosomes when added to cell homogenates, raising the possibility that its antitumoral effect may be mediated by endocytosis and lysosomes.