Cell specificity of rat cytokeratin p39 during azo dye-induced hepatocarcinogenesis

Monoclonal or affinity-purified antibodies specific to Novikoff hepatoma cytokeratin p39 were employed to study the origin and fate of p39-containing cell types during hepatocarcinogenesis induced with N,N-dimethyl-p(m-tolylazo)aniline. Frozen sections were obtained from the livers of animals autopsied temporally during carcinogen feeding and were assayed immunohistochemically. In normal, untreated liver or in liver from animals fed the hepatotoxin alpha-naphthyl-isothiocyanate, the localization of p39 was restricted to bile duct epithelial cells while hepatocytes were non-reactive. However, during carcinogen treatment we observed a sequential appearance of immunoreactive cells which were similar morphologically to the classical 'oval' cells of hepatocarcinogenesis; eventually these cell types were enriched around the preneoplastic hepatocyte nodules. Occasional transformed hepatocytes within the nodules exhibited strong immunoreactivity. In the later stages of hepatocarcinogenesis, these antibodies stained the epithelial cells in areas of severe adenosis as well as the neoplastic epithelial cells of cholangiomas and some, but not all, hepatocellular carcinomas. Our results document the presence of p39 in the 'oval' cells of hepatocarcinogenesis and indicate that some populations of transformed hepatocytes exhibit this cytokeratin after transformation.