Functional markers and growth behavior of preneoplastic hepatocytes.

Functional markers and growth behavior of abnormal hepatocytes at several stages of liver carcinogenesis were studied. Early lesions, i.e., hyperplastic foci and areas, did not accumulate iron in siderotic livers, had persistent glycogen stores, were not more agglutinable by concanavalin A, and were associated with alpha-fetoprotein secretion, but were not independent secretors of high amounts. The cells in the early lesions had an increased mitotic index, but cells from livers with early lesions did not have an increased survival in cell culture or the ability to grow in soft agar. The more developed lesions, hyperplastic nodules, also did not store iron, had persistent glycogen, did not display increased concanavalin A agglutinability, and were not independent secretors of high levels of alpha-fetoprotein. Similarly, nodule cells were proliferative but did not display an increase in survival in cell culture. In addition, both iso- and autotransplantation of nodules into mammary fat pads resulted in persistence but not growth of nodule cells. On the other hand, hepatocellular carcinomas regularly grew upon transplantation. Thus, early lesions and hyperplastic nodules were proliferative lesions did not possess autonomous growth capability comparable to that of hepatocellular carcinomas.