LIVER-TUMORS AND POSSIBLE PRENEOPLASTIC LESIONS, INDUCED BY A FOOD-DERIVED HETEROCYCLIC AMINE IN CYNOMOLGUS MONKEYS - A STUDY OF HISTOLOGY AND CYTOKERATIN EXPRESSION

A food-derived mutagenic heterocyclic aromatic amine, 2-amino-3-methyl imidazo[4,5-f]quinoline (IQ), is a potent hepatocarcinogen in cynomolg us monkeys. In an ongoing carcinogenesis study, 34 out of 40 monkeys d osed with IQ have developed malignant liver tumors. The histology and cytokeratin expression was examined in a total of 94 tumors and non-ne oplastic lesions obtained from 34 cases. The majority of the tumors we re classified as hepatocellular carcinoma. In some cases, a striking d ifference in the histological features between individual tumor nodule s was suggestive of a multicentric origin. Intrahepatic vascular invas ion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatoce llular carcinoma cases. There was no evidence of regenerative hyperpla sia or fibrosis in the parenchyma of the tumor-bearing livers. Clear-c ell foci composed of glycogen-rich hepatocytes were the only macroscop ic lesions detected prior to gross tumor development. Other liver lesi ons included dysplastic hepatocyte foci and areas of proliferating bil e ductular like (oval) cells, located around the periportal areas and along the portal tracts. Expression of bile duct type cytokeratin 7 wa s observed in a few of the oval cells and non-malignant hepatocytes, a s well as in some of the hepatocellular carcinoma nodules. This aberra nt cytokeratin expression raises questions concerning the histogenesis of the IQ-induced hepatocellular carcinoma.