α-Fetoprotein secretion by injured and regenerating hepatocytes in the dog

Both hepatic injury and partial resection are followed by elevation of serum α-fetoprotein (AFP). However, whether injured or regenerating hepatocytes are the site of AFP secretion remains controversial. The effects of 3.5 hr of selective hepatic ischemia to the left (L) lobes (70% hepatic mass) of the canine liver on AFP production and liver regeneration by both L and right (R) hepatic lobes are reported. Twenty-one experimental and 13 control animals were studied. AFP was measured by radioimmunoassay in liver tissue homogenates and serum from both systemic and hepatic venous blood obtained preoperatively and on postoperative Days 2, 4, 6, 7, and 8. Tissue AFP was also assessed by immunofluorescent staining. Hepatic regeneration was quantified by autoradiography and DNA specific activity following the intravenous administration of [ 3H]thymidine. AFP levels were increased above baseline by postoperative Day 4 in biopsies taken from both L and R liver lobes with peak values occurring on Day 7. Immunofluorescent staining confirmed the presence of intracellular AFP in hepatocytes of both R and L lobes on postoperative Days 2 through 6. Serum AFP became significantly elevated above preoperative values by Day 4 and maximal on Day 6. No difference was observed in AFP levels in systemic, L, or R hepatic venous blood. Hepatocellular DNA synthesis was increased on postoperative Days 2 through 8 in both R and L liver lobes. In conclusion, selective hepatic ischemia results in AFP secretion by both injured and uninjured liver lobes. These results suggest that both regenerating and injured hepatocytes synthesize AFP in the dog.