CONTROL OF CELL GROWTH BY TISSUE AND SERUM FACTOR

KCl extracts from rat kidney, rat liver, and Morris hepatomas inhibited ('3)H-thymidine incorporation into cultured cells. The most pronounced inhibition was achieved with the kidney extract. ('3)H-thymidine incorporation was inhibited almost immediately after the addition of the extract. Twenty-four hours after removal of the inhibitor ('3)H-thymidine incorporation was restored. Although incorporation of ('3)H-deoxycytidine and cell growth were inhibited, protein synthesis was not inhibited by KCl extract. The inhibitor was stable to heat (80(DEGREES)C for 10 minutes). Exposure of the extract to proteolytic enzymes, hyaluronidase and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis. The inhibitor appeared to be a mucoprotein. The carbohydrate moiety may be responsible for the inhibition. Evidence was provided that the primary action of the inhibitor appears to be inhibition of thymidine phosphorylation.;A normal serum protein disappears from the serum of animals bearing Morris hepatomas 7777 and 5123 as the tumors increase in size. Serum factor levels are increased well over those found in normal rats 24 hours after partial hepatectomy. Increased levels persist for 12 days following partial hepatectomy. The serum protein is also increased following injections of T(,3) and is decreased in thyroidectomized animals. Elevated levels of T(,3) are correlated with elevated levels of the serum protein and both are correlated with increased hepatic DNA synthesis. Low levels of T(,3) as a result of thyroidectomy are followed by low levels of serum protein resulting in a diminished capacity for hepatic DNA synthesis and decreased hepatoma growth. T(,3) injections restored the capacity for hepatic DNA synthesis and hepatoma growth.;Injection of purified serum factor into normal rats resulted in increased ('3)H-thymidine incorporation in liver cells. Hepatoma growth was higher in rats that had elevated serum factor levels at the time they received a hepatoma transplant. It is suggested that the synthesis of this serum protein is stimulated by T(,3) and hepatocyte proliferation and hepatoma growth are influenced by the serum protein. The serum protein might be a humoral factor influencing metabolic events in hepatocytes and hepatomas or it might be a carrier for an agent that in turn has a direct effect on these tissues.