Histological and enzymatic changes in the livers of rats fed the hepatic carcinogen diethylnitrosamine

Abstract

When the liver carcinogen diethylnitrosamine (DENA) was fed to Wistar rats in their drinking water over a period of 5 months, two main changes in liver structure were observed to develop in sequence: first the gradual formation of hepatomas (circumscribed nodules of highly abnormal parenchymal cells); later cholangiomas (progressive overgrowth of bile duct epithelium) which eventually dominated the histological picture. Specific and non-specific histidine decarboxylase activities were measured in livers of treated and control animals at regular intervals, the two enzymes being characterized by their Michaelis constants, pH optima, effect of benzene, and effect of inhibitors. The results indicate that the specific decarboxylase (pH 6.5) is associated with the period of hepatoma formation (maximal in excised hepatoma tissue) and not with proliferation of bile duct epithelium (cholangioma). The enzyme is thus associated with the growth of a particular cell rather than with growth in general. In the livers of both control and DENA-treated rats a highly significant positive correlation was observed between the histidine decarboxylase activity at pH 8 and the dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) decarboxylase activities; this suggests that these three activities are due to a single enzyme, a non-specific aromatic amino acid decarboxylase.