The effect of liver cytosol on hepatic regeneration and tumor growth.

This report further evaluates the concept that the interaction of factors that originate within the liver can contribute, regulate or even initiate the actual development of hepatic regeneration after liver cell necrosis or partial hepatectomy. The effect of liver cytosol (100,000 g supernatant), both from intact adult rat liver (NLC) and from adult rat liver remnants that had been regenerating for 24 hours after 70% partial hepatectomy (PH) in posthepatectomy liver regeneration in the rat was studied. The specificity of the growth-controlling properties in liver cytosol was determined using tumor cells. The intraperitoneal administration of NLC after PH resulted in approximately 70-80% inhibition of the peak 3H-DNA specific activity seen in controls at 18 and 24 hours post-PH, with a significant increase in DNA synthesis at 31-40 hours post-PH. The intraperitoneal administration of RLC after PH, augmented the hepatic regenerative response normally produced. Autoradiographic determination of hepatic nuclear labeling confirmed the inhibitory and stimulatory properties of NLC and RLC respectively. Syngeneic NLC or RLC at six and 24 days after subcutaneous tumor inoculation resulted in significant inhibition of tumor growth for both a methylcholanthrene-induced bladder carcinoma (FBCa) and an HTC-hepatoma. The retardation of FBCa growth could be enhanced by administering NLC or RLC every three or seven days. Syngeneic and xenogeneic liver cytosol resulted in dose-dependent inhibition of P815 mastocytoma cell proliferation in vitro. It is apparent from these studies that both stimulatory and inhibitory factors can be extracted from liver tissue that not only influence liver cell regeneration, but also affect tumor growth. Further isolation and characterization of these factors may lead to an understanding of more fundamental problems such as the control of normal and malignant cell growth.