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Sequential Phenotypic and Biochemical Alterations during Chemical Hepatocarcinogenesis¹

Department of Pathology, New York University Medical Center, New York, New York 10016

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.

¹ Presented at the Conference "Early Lesions and the Development of Epithelial Cancer," October 21 to 23, 1975. Bethesda, Md. This work was supported by Research Grants CA-15859 and CA-12141 from the National Cancer Institute, NIH.