Changes in the zonation of lactate dehydrogenase activity in lobules of rat liver after experimentally induced colon carcinoma metastases.

Visualization of lactate dehydrogenase (LDH) activity with Neotetrazolium as final electron acceptor under anaerobic conditions and an incubation medium containing polyvinyl alcohol showed that under normal physiological conditions a zonal distribution of LDH activity is present in the liver lobule of male rats. Periportal hepatocytes contain more LDH activity than pericentral hepatocytes. This difference is due to the role of LDH both in gluconeogenesis (periportal cells) and glycolysis (pericentral cells). In livers containing metastases from colon carcinoma, areas of the parenchyma which are not affected by tumour growth maintain such zonation in the lobule, whereas areas close to metastatic foci show increased activity which is distributed uniformly over the lobule. This change may be explained by a Cori's cycle-like relationship between malignant cells and the surrounding hepatocytes due to glucose consumption and lactate production by the tumour cells. Within the metastatic foci, a zonation of LDH activity was also observed. Malignant cells close to the edge of the tumours contained the lowest activity, whereas activity increased inwards. Cancer cells directly surrounding necrotic areas showed the highest activity. Such patterns are in line with increasing anaerobic glycolysis towards the inner metastatic regions. Anaerobic glycolysis supplies limited amounts of ATP with concomitant lactate production but also large amounts of metabolites for RNA, DNA, lipid and complex carbohydrate synthesis. Lactate that is produced by the metastases induces adaptive changes in surrounding hepatocytes to convert this excess of lactate effectively.