Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats.

Alpha-fetoprotein (AFP) in the sera of 35 LEC (Long-Evans with a cinnamon-like coat color) rats between 7 and 25 weeks of age was evaluated by enzyme-linked immunosorbent assay (ELISA). Elevation of serum AFP and proliferation of oval cells in the liver were observed in most LEC rats, which suffered from acute hepatitis. On the other hand, the serum AFP level was within the normal range before the onset of hepatitis. Immunohistochemical staining for AFP revealed that some of the proliferating oval cells produced AFP. Morphometric analysis of AFP-positive cells and ELISA for serum AFP demonstrated that there was a statistically significant correlation between the number of AFP-positive cells in the liver and the concentration of AFP in the serum. Histological examination revealed the transition and differentiation of the oval cells to small hepatocytes. These results suggested that the phenomena which occurred in LEC rats suffering from acute hepatitis were similar to those that occurred during the early stage of azo dye hepatocarcinogenesis, although the extent of the oval cell proliferation and the elevation of serum AFP in LEC rats were not as great as those in rats treated with azo dye. This is the first report on a rat strain with proliferation of AFP-producing oval cells during its natural history.