INFLUENCE OF EPIDERMAL GROWTH-FACTOR ON LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN MICE

The role of epidermal growth factor (EGF) in liver regeneration was studied in mice after partial hepatectomy. Two weeks before partial hepatectomy, mice were sham-operated (control) or sialoadenectomized (removal of submandibular glands) to reduce plasma EGF levels. Sialoadenectomized mice showed low plasma EGF levels (29.7 +/- 6.6 pmol/l; mean +/- S.E.M.) compared with controls (66.0 +/- 8.3 pmol/l). After partial hepatectomy, sialoadenectomized mice were treated with or without a daily s.c. injection of 5-mu-g EGF and the rate of DNA synthesis in the regenerating liver was monitored by [I-125]iododeoxyuridine uptake. Control mice showed a sharp peak of DNA synthesis at 48 h after partial hepatectomy while sialoadenectomized mice showed a delayed and broad peak at 84 h. Treatment of sialoadenectomized mice with EGF (5-mu-g/mouse per day) completely restored the pattern of DNA synthesis so that a sharp peak appeared at 48 h. The total liver DNA content of the control mice (79.1 +/- 2.5% of the preoperative level; mean +/- S.E.M.) was significantly (P < 0.01) higher than that of the sialoadenectomized mice (65.2 +/- 3.0%) 3 days after partial hepatectomy, but this difference disappeared on day 7 when liver regeneration was almost completed in both groups. Treatment of sialoadenectomized mice with EGF increased total liver DNA content (78.2 +/- 2.9%) to that of control mice on day 3 after partial hepatectomy. In addition, normal mice showed a rapid increase in plasma EGF levels at 1-8 h after partial hepatectomy, whereas sialoadenectomized mice showed low plasma EGF levels throughout the course of the experiment. These results suggest that EGF derived from the submandibular glands plays a role in promoting the early stage of liver regeneration.