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

observed also with many tumor-associated antigens, such as a-fehoprotein and carcinoembryonic antigen (3). Al though the phenotypes, including isozyme pattern, in the transplantable humors are known ho be fairly stable through generations of transplantation (1, 17, 50), in certain in stances some phenotypes in Imansplanhablehepahomas alter gradually or suddenly along with increased growth male during successive transplantations (1, 22, 25, 50). However, it is also strongly supposed that enzymes in transplantable hepatomas do not deviate simultaneously or in ordered progression as they do in embryonic development. Some enzymes, such as those in amino acid metabolism (10, 20), in the urea cycle, and in the synthesis of nucleic acid precursors (13, 23, 41), deviate with no relation to growth mateor differentiation. Although key enzymes of glycolysis and gluconeogenesis show common ordered deviation pal hems with increased growth mateand decreased diffemenhia lion (47), enzymes such as lactate dehydmogenase (26) and glucose-6-phosphate dehydrogenase (21, 46, 47) deviate apparently at random with no relation ho growth rate or differentiation. We also reported that some Yoshida asciles hepahomas, although poorly differentiated, have exception ally predominant activities of the liver-type isozyme of phosphorylase (28). Therefore, it is very important hoextend the findings hitherto obtained with transplantable hepaho mas hoascertain, in the precancerous stales of the liver and primary hepahomas, ho what degree these enzyme allema lions are ordered, how specific they are ho hepalomas, and at what stage they are fixed during hepalocarcinogenesis. Such studies on enzyme alterations in the precancerous slates and primary hepatomas are necessary not only ho understand mechanisms of hepahocarcinogenesis but also for clinical application, e.g., for enzymatic diagnosis on biopsy specimens. In this study we measured simultane ously the activities of 9 enzymes of carbohydrate metabo lism, and in 4 of these the isozyme activities were measured kinehically and immunochemically in individual liver nod ules and primary hepatomas induced by 2-FAA,3 DENA, or 3'-Me-DAB. In this paper we confirm in primary hepahic nodules and hepalomas the same general enzyme deviation patterns that are seen in transplantable hepatomas. We also observed differences among the 3 carcinogens in their potential ho induce more dedifferenhiated hepalomas with marked deviation. We also found that in some nodules and hepalomas the liver-specific isozyme of some enzymes was retained, whereas in most other nodules and hepatomas the enzyme pattern deviated from that of the liver.