Sequential phenotypic and biochemical alterations during chemical hepatocarcinogenesis.

Chronic exposure to chemical carcinogens induces in the target tissue a series of complex morphological and biochemical alterations that precede the appearance of overt cancer. Three types of experiments are described: (a) exposure of livers that had received subcarcinogenic doses of N-2-fluorenylacetamide to a subcarcinogenic dose of dimethylnitrosamine resulted in a 100% yield of neoplastic nodules and hepatocellular carcinoma: (b) neither normal hepatocytes nor those obtained from neoplastic nodules were agglutinated by any of the lectins tested. This finding was also true for slowly growing cells from carcinomas, while those of rapidly growing carcinomas were agglutinated by several lectins; (c) analysis of nonhistone proteins isolated from neoplastic nodules demonstrated the appearance of many new species in euchromatin when compared with normal liver. Carcinomas demonstrated an even greater number of new species and they were demonstrated in heterochromatin as well.