Specific inhibition of proliferation of nonmalignant rat hepatic cells by a factor from rat liver.

A simple quantitative assay based on the colony-forming ability of cells was used to investigate the effect of partially purified factors isolated from rat liver on the proliferation of nonmalignant and malignant rat liver epithelial cells in culture. Using this assay, which differentiates between the cytostatic and cytotoxic actions of the test materials, we found that the liver factors exerted a dose-dependent cytostatic inhibition of nonmalignant liver cells but had no inhibitory effect on malignant liver cells. However, the crude fractions showed a significant activation of the proliferation of one of the malignant cell lines tested. The inhibitory effect of this material was not due to arginase, thymidine, or thymidine-degrading enzymes. The respective inhibitory and activating effects exerted by very low concentration of the liver fractions could not be resolved by our separation methods. Even though the material may contain a mixture of activators and inhibitors, it is likely that the differential effect on the proliferative capacity of nonmalignant and malignant cells is due to the altered state of the malignant cells.