Biological significance of AFP-positive cells in rat livers with hyperplastic nodules induced by 3'-Me-DAB; combined immunocytochemical and radioautographical studies.

We investigated alpha-fetoprotein (AFP)-positive cells in 3'-Me-DAB hepatocarcinogenesis. In the early stage of 3'-Me-DAB hepatocarcinogenesis immunoreaction of AFP was detected in proliferating cholangiolar "oval" cells and in the late stage, AFP-positive cells, differing from oval cells, were detected in clusters in rat liver with hyperplastic nodules. The clusters of AFP-positive cells were morphologically classified into two different types of foci and one type of nodule. The combined techniques of immunocytochemistry and ratioautography revealed that AFP-positive foci and nodule had more 3H-thymidine labeling index than did areas without AFP-positive cells in liver with hyperplastic nodules; also one type of AFP-positive foci had a higher labeling index than the other type and in AFP-positive nodules there was active cell proliferation; but AFP-positive foci or nodules had less 3H-thymidine labeling than AFP-positive hepatoma cells. These findings suggested that AFP-positive foci and nodule had different biological significance in development of hepatocellular carcinoma and that AFP-positive foci with higher labeling index and AFP-positive nodule should be surveyed as preneoplastic population.