Humoral inhibitor of rat hepatocyte DNA synthesis from patients with fulminant liver failure

✍ Scribed by Haruki Yamada; Gotaro Toda; Makoto Yoshiba; Naoaki Hashimoto; Yusei Ikeda; Hiroshi Mitsui; Kiyoshi Kurokawa; Fumio Sugata; Robin D. Hughes; Roger Williams

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 856 KB
• Volume: 19
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840190510

✦ Synopsis

Sera and ultrafiltrates (relative molecular mass < 10,000 Da) from patients with fulminant liver failure inhibit hepatocyte DNA synthesis in vivo. In this study the effects of ultrafiltrates from pooled sera from fulminant liver failure patients in the United Kingdom and plasma ultrafiltrates from fulminant liver failure patients in Japan have been investigated in primary cultured rat hepatocytes, with incubation for up to 72 hr. Both types of ultrafiltrate inhibited the incorporation of [3H]thymidine into acid-precipitable material and reduced the cell labeling index as determined on autoradiography in hepatocytes stimulated by epidermal growth factor and insulin compared with normal serdplasma ultrafiltrates. The inhibitory effects observed were dose dependent, reversible when the fulminant liver failure ultrafiltrate was removed and were not associated with increased release of lactate dehydrogenase or suppression of protein synthesis as assessed on the basis of the incorporation of [3H]leucine. The effects appeared to be specific for hepatocytes; in preliminary experiments DNA synthesis was not inhibited in cultured fibroblasts (NJH 3T3 cells). These experiments are further evidence of the presence of an inhibitory factor of relative molecular mass less than 10,000 Da in the blood of patients with fulminant liver failure. (HEPATOLOGY 1994;19: 1133-1 140.)

The liver possesses a remarkable capacity to regenerate after surgical or toxic insult (1-3). In fulminant