Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver.

1. The elucidation of the biochemical controls of growth processes is basic to understanding both normal and malignant growth. The exquisitely sensitive control demonstrated in the regenerating liver provides an excellent model system for growth studies. 2. Intraperitoneal injection of an extract from weanling rat liver into 34% hepatectomized rats stimulates [3H]thymidine incorporation into recipient hepatic DNA 2.5-fold. This stimulation is seen after a 10 hr lag period. 3. Extracts from weanling rat liver contain the highest level of the hepatic regenerative stimulator substance (SS), whereas extracts from adult liver give no significant stimulation. 4. If adult rats are partially hepatectomized, SS is demonstrated in their livers 12-15 hr after hepatectomy. 5. Partial characterization of SS shows that it is a soluble material not sedimented by centrifugation for 2 hr at 145,000 g. The stimulator activity is stable to heating at 65 degrees C and 100 degrees C for 15 min but is lost when treated with 10% perchloric acid.