Different deviation patterns of carbohydrate-metabolizing enzymes in primary rat hepatomas induced by different chemical carcinogens.

Abstract

The deviation patterns of nine enzymes of carbohydrate metabolism were examined simultaneously in the individual hyperplastic liver nodules and primary hepatomas induced by N -2-fluorenylacetamide, diethylnitrosamine, and 3′-methyl-4-dimethylaminoazobenzene, and the activities were considered according to the histological classification of the tissues. With decreased histological differentiation, the liver-specific marker enzymes of gluconeogenesis, glucose-6-phosphatase and fructose-1,6-bis-phosphatase, as well as the hepatic isozymes of glucose-adenosine 5′-triphosphate phosphotransferase, pyruvate kinase, aldolase, and glycogen phosphorylase, decreased gradually and were replaced with the respective nonhepatic fetal or prototypic isozymes of undifferentiated tissues. In poorly differentiated hepatomas, glycogen synthase was also decreased and phosphofructokinase was increased. Glucose-6-phosphate dehydrogenase increased remarkably from nodular hyperplasia with no relation to differentiation. The degree of enzyme deviation from the adult male liver differed among hepatomas induced by the different carcinogens, especially between those induced by N -2-fluorenylacetamide (or diethylnitrosamine) and 3′-methyl-4-dimethylaminoazobenzene, reflecting the difference in potential of the three carcinogens to induce the more dedifferentiated hepatoma. These differences were most evident in the isozyme deviation patterns of glucose-adenosine 5′-triphosphate phosphotransferase and pyruvate kinase. Some of the nodules and hepatomas retained exceptionally high activities of some hepatic isozymes, especially of the liver type of pyruvate kinase, near or above the normal level.