Rat hepatocellular carcinogenesis and proliferating cell nuclear antigen expression induced by...

The experimental conditions for the induction of rat hepatocellular carcinoma by oral administration of 3'-methyl-4-dimethylaminoazobenzene (DAB) were established. Hematoxylin-eosin (HE) staining of the liver sections revealed that precancerous lesions, characterized by small proliferation nest, hyperplastic nodule, oval cell and adenofibrosis, were observed 2 months after DAB administration. The highest incidence of hepatocellular carcinoma, trabecular carcinoma and mixed form of hepatocellular and cholangiocarcinoma was observed after 3-5 months and remained for an additional 2 months, even if the rats were continuously fed with DAB-free fodder. Immunohistochemical study with monoclonal antibody against proliferation cell nuclear antigen (PCNA) revealed that the relative number of PCNA-positive cells increased with the progress of the carcinoma. The present study confirms the previously reported usefulness of the PCNA immunostaining method for prognosis and assessment of the malignancy of carcinoma.