HUMORAL INHIBITOR OF RAT HEPATOCYTE DNA-SYNTHESIS FROM PATIENTS WITH FULMINANT LIVER-FAILURE

Sera and ultrafiltrates (relative molecular mass < 10,000 Da) from pat ients with fulminant liver failure inhibit hepatocyte DNA synthesis in vivo. In this study the effects of ultrafiltrates from pooled sera fr om fulminant liver failure patients in the United Kingdom and plasma u ltrafiltrates from fulminant liver failure patients in Japan have been investigated in primary cultured rat hepatocyte, with incubation for up to 72 hr. Both types of ultrafiltrate inhibited the incorporation o f [H-3]thymidine into acid-precipitable material and reduced the cell labeling index as determined on autoradiography in hepatocytes stimula ted by epidermal growth factor and insulin compared with normal sera/p lasma ultrafiltrates. The inhibitory effects observed were dose depend ent, reversible when the fulminant liver failure ultrafiltrate was rem oved and were not associated with increased release of lactate dehydro genase or suppression of protein synthesis as assessed on the basis of the incorporation of [H-3]leucine. The effects appeared to be specifi c for hepatocytes; in preliminary experiments DNA synthesis was not in hibited in cultured fibroblasts (NM 3T3 cells). These experiments are further evidence of the presence of an inhibitory factor of relative m olecular mass less than 10,000 Da in the blood of patients with fulmin ant liver failure.