Mitogenic activity in platelet-poor plasma from rats with persistent liver nodules or liver cancer

• Published in: Biochemical and biophysical research communications Vol. 148; no. 1; pp. 449 - 455
• Main Authors: Semple, E., Hayes, M.A., Rushmore, T.H., Harris, L., Farber, E.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 14.10.1987; Elsevier
• Subjects: Animals; Applied sciences; Blood Platelets - physiology; Cells, Cultured; DNA Replication; ErbB Receptors - metabolism; Exact sciences and technology; Interphase; Kinetics; Liver - cytology; Liver - metabolism; Liver Neoplasms, Experimental - blood; Male; Other techniques and industries; Precancerous Conditions - blood; Rats; Rats, Inbred F344; partial hepatectomy; Williams E medium; PBS; TdR; EGF; L1; DENA; WE; PPP; BSA; diethylnitrosamine; TGF; phosphate buffered saline; PH; labeling index; thymidine; platelet-poor plasma; epidermal growth factor; transforming growth factor; bovine serum albumin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(87)91132-6

Platelet-poor plasma (PPP) from F-344 rats with chemically-induced preneoplastic liver nodules or hepatocellular carcinoma stimulated S-phase DNA synthesis in monolayer cultures of normal rat hepatocytes. Similar mitogenic activity was detected in PPP 6 hrs to 1 week after partial hepatectomy (PH) or after necrotizing doses of CCl 4 or diethylnitrosamine (DENA). Very little activity was found in PPP from control rats. The mitogenic activity in PPP from animals with nodules was nondialyzable (> 14 kd) and bound to a heparin-sepharose affinity column. None of the mitogenic PPPs competed with [ 125I] epidermal growth factor (EGF) for binding sites on A431 cells or normal rat hepatocytes. These studies indicate that persistent proliferation of preneoplastic and neoplastic hepatocytes is associated with increased circulating levels of mitogenic hepatocyte growth factor.