Strain and species differences in susceptibility to liver tumour induction

Abstract

Strain and species differences have frequently been reported in the incidence of spontaneous liver tumours and in the response of the liver to chemical carcinogens. Tentative explanations for these strain and species differences in hepatocarcinogenesis, such as variations in metabolic activation of the chemicals or differing capacities for repair of carcinogen-induced damage of DNA, have been offered, but many discrepancies are obvious. As demonstrated mainly in the rat, hepatotropic carcinogens may hit at least four different types of target cell in the liver, namely, the hepatocytes, the bile ductular epithelia, the sinusoidal lining cells and the perisinusoidal cells. All of these cell types may undergo characteristic, carcinogen-induced changes and give rise to tumours or tumour-like lesions: hepatocellular carcinomas or adenomas (frequently called 'neoplastic' or 'hyperplastic' nodules), cholangiocellular tumours (cystic cholangiomas, cholangiofibromas, cholangiocarcinomas), benign and malignant haemangioendotheliomas and spongiosis hepatis. The results of investigations on the pathogenesis of the different tumour types suggest that the sequence of cellular and subcellular changes occurring during the development of the tumours is in principle identical in different species, including primates. From experimental studies of hepatocarcinogenesis, a close connection between a carcinogen-induced, persistent hepatocellular glycogenosis and the neoplastic transformation of hepatocytes has been postulated. This hypothesis is supported by an increasing number of reports of the appearance of hepatic tumours in people suffering from inborn hepatic glycogenosis.