REDUCED AUTOPHAGIC ACTIVITY IN PRIMARY RAT HEPATOCELLULAR-CARCINOMA AND ASCITES HEPATOMA-CELLS

Autophagy, measured as the sequestration of an endogenous cytosolic en zyme (LDH), showed a progressive rate reduction during diethylnitrosam ine-induced rat liver carcinogenesis. In primary hepatocellular carcin omas the autophagic activity was only one-fourth of that seen in norma l hepatocytes. Reduced autophagy was also observed in peritumorous hep atocytes and in cells from preneoplastic liver, and a complete suppres sion of autophagic protein degradation was seen in normal hepatocytes treated with ascitic fluid from an ascites hepatoma, suggesting that t umour cells and their precursors may produce autophagy-suppressive fac tors with an autocrine and paracrine action. In cells from the transpl antable rat ascites hepatoma, Yoshida AH-130, autophagic activity was negligible during active (logarithmic) growth, but increased to simila r to 0.4%/h at high cell density, i.e. in stationary phase. In contras t to normal hepatocytes, autophagy in the AH-130 cells was not inhibit ed by ascitic fluid. The hepatoma cells would thus appear to have lost some aspects of autophagy regulation while retaining others. However, even the highest rate of hepatoma cell autophagy was only one-tenth o f the maximal activity seen in normal hepatocytes, confirming the hypo thesis that reduced autophagy may be an important aspect af growth der egulation in liver cancer.