Studies on the specificity of tissue supernatants on the proliferation of liver in baby-rats.

Supernatants (105,000 g) prepared from extracts of liver and kidney were injected at different concentrations into 10 day-old rats and the resulting effects on 3H-thymidine incorporation in liver, kidney and lung were measured over a period of 24 hours. Incorporation in all three organs is inhibited by supernatants from both liver and kidney, with maximal activity between 12 and 18 hours after injection. Fractions prepared from liver supernatant by ultrafiltration and alcohol precipitation also showed no specific effect on liver cells. In order to test whether the activity of any factors in the supernatants is cell-cycle dependent, organs of baby rats were synchronized by two different procedures: a) injection of a 3.5% casein solution, b) injection of hydroxyurea (2 x 10 mg/kg body weight with an internal of one hour). Inhibitory effects were only observed when the supernatants were injected during the G1-phase of the target cells. Supernatants prepared in a similar way from other organs such as spleen, lung or heart also inhibited thymidine incorporation in casein-stimulated liver from baby rats. All of our investigations have therefore failed to find any indication of tissue-specific activity in these extracts.