Summary
Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetyl-aminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demosntrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate, a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Altmann HW (1978) Pathology of human liver tumors. In: Remmer H, Bolt H, Bannasch P, Popper H (eds) Primary liver tumors. Proceedings of the 25th Falk Symposium, Titisee 1977. MTP Press, Lancaster, pp 53–71
Bannasch P (1968) The cytoplasm of hepatocytes during carcinogenesis. Re Res Cancer Res 19:1–100
Bannasch P (1984) Sequential, cellular changes during chemical carcinogenesis. J. Cancer Res Clin Oncol 108:11–22
Bannasch P (1986) Preneoplastic lesions as end points in carcinogenicity testing. I. Hepatic preneoplasia. Carcinogenesis 7:689–695
Bannasch P, Angerer (1974) Glykogen und Glukose-6-Phosphatase während der Kanzerisierung der Rattenleber durch N-Nitrosomorpholin. Arch Geschwulstforsch 43:105–114
Bannasch P, Klinge O (1971) Hepatocellulãre Glykogenose und Hepatombildung beim Menschen. Virchows Arch (Pathol Anat) 352:157–164
Bannasch P, Hacker HJ, Klimek F, Mayer D (1984) Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis. Adv Enzyme Regul 22:97–121
Bannasch P, Müller HA (1964 Lichtmikroskopische Untersuchungen über die Wirkung von N-Nitrosomorpholin auf die Leber von Ratte und Maus. Arzneim Forsch (Drug Res) 14:805–814
Berenblum I, Shubik P (1947) The role of croton oil application, associated with a single painting of a carcinogen, in tumor induction of the mouse's skin. Br J Cancer 1:379–382
Brinkmann A, Katz N, Sasse D, Jungermann K (1978) Increase of gluconeogenic and decrease of glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy. Hoppe Seylers Z Physiol Chem 359:1561–1571
Cameron R, Kellen J, Kolin A, Malkin A, Farber E (1978) γ-Glutamyltransferase in putative premalignant liver cell populations during hepatocarcinogenesis. Cancer Res 38:823–829
Coggin JH Jr, anderson NG (1974) Cancer, differentiation and embryonic antigens: Some central problems. Adv Cancer Res 19:105–166
Crisp DM, Pogson CJ (1972) Glycolytic and gluconeogenic enzyme activities in parenchymal and non-parenchymal cells from mouse liver. Biochem J 126:1009–1023
Criss WE (1971) A review of isozymes in cancer. Cancer Res 31:1523–1542
Eigenbrodt E (1986) New aspects of carbohydrate metabolism in tumor cells. Food Chem Toxicd 23:863
Emmelot P, Scherer E (1980) The first relevant cell stage in rat liver carcinogenesis. Biochim Biophys Acta 605:247–304
Enomot K, Farber E (1982) Kinetics of phenotypic maturation of remodeling of hyperplastic nodules during liver carcinogenesis. Cancer Res 42:2330–2335
Farber E (1984a) Cellular biochemistry of the stepwise development of cancer with chemicals: G.H.A. Clowes memorial lecture. Cancer Res 44:5463–5474
Farber E (1984b) Chemical carcinogenesis: a current biological perspective. Carcinogenesis 5:1–5
Farber E (1984c) The multistep nature of cancer development. Cancer Res 44:4217–4223
Farber E, Cameron RG (1980) The sequential analysis of cancer development. Adv Cancer Res 31:125–226
Fischer G (1986) Increased UDP-glucuronyltransferase and gamma-glutamyltranspeptidase in enzyme-altered rat liver lesions produced by low doses of aflatoxin B1. Virchows Arch (Cell Pathol) 51:443–460
Fischer G, Katz N, Fischer W, Schauer A (1982a) Biochemical quantification on ATPase activities during liver carcinogenesis. Cancer Detect Prev 5:73
Fischer G, Katz N, Fischer W, Schauer A (1982b) Mikrodissektion und Mikroanalytik an Frühstadien der chemischen Leberkan-zerogenese. Verh Dtsch Ges Pathol 66:471
Fischer G, Schauer A, Katz N (1982c) Fascilitation of microdissection by use of a new microscopic and micromanipulatory unit. Naturwissenschaften 69:146
Fischer W, Ick M, Katz NR (1982) Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus. Z Physiol Chem 363:375–380
Fischer W, Wagle S, Katz NR (1983) Altered distribution of hexokinase and glucokinase between parenchymal and non-parenchymal cells of rat liver after methapyrilene intoxication. Biochem Biophys Res Commun 115:1090–1095
Fischer G, Lilienblum W, Ullrich D, Bock KW (1986a) Immunohistochemical differentiation of γ-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens. Carcinogenesis 7:1405–1410
Fischer G, Hartmann H, Droese M, Schauer A, Bock KW (1986b) Histochemical and immunohistochemical detection of putative preneoplastic liver foci in women after long-term use of oral contracetives. Virchows Arch (Cell Pathol) 50:321–337
Fischer G, Eigenbrodt E, Lodder D, Katz N, Reinacher M (1987) Immunohistochemical demonstration of decreased l-pyruvate kinase in enzyme altered rat liver lesions produced by different carcinogens. Virchows Arch (Cell Pathol) (in press)
Friedrich-Freksa H, Gössner W Börner P (1969) Histochemische Untersuchungen der Cancerogenese in der Rattenleber nach Dauergaben von Diäthylnitrosamin. Z Krebsforsch 72:226–239
Gössner W, Friedrich-Freksa H (1964) Histochemische Untersuchungen über die Glucose-6-Phosphatase in der Rattenleber während der Cancerisierung durch Nitrosamine. Z Naturforsch 19b:862–869
Grisham JW (1962) A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver, autoradiography with thymidine-H3. Cancer Res 22:842–849
Hacker HJ, Moore MA, Mayer D, Bannasch P (1982) Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver. Carcinogenesis 3:1265–1272
Kalengay MMR, Desmet VJ (1978) Gamma-glutamyl transferase as oncofetal marker of experimental hepatocarcinogenesis in the rat. Scand J Immunol 8:547–556
Katz N, Teutsch H, Jungermann K, Sasse D (1977) Heterogenous reciprocal localization of fructose-1,6-bisphosphatase and of glucokinase in microdissected periportal and perivenous rat liver tissue. FEBS Lett 83:272–276
Klimek F, Mayer D, Bannasch P (1984)_Biochemical microanalysis of glycogen content and glucose-6-phosphatate dehydrogenase activity in focal lesions of the rat liver induced by N-nitrosomorpholine. Carcinogenesis 5:265–280
Lowry O, Passonneau J (1972) A flexible system of enzymatic analysis. Academic Press, New York
Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605:191–215
Reinacher M (1985) Immunohistochemical demonstration of pyruvate kinase isoenzyme type L as a new and early marker during rat liver carcinogenesis. Food Chem Toxicol 23:865
Reinacher M, Eigenbrodt E, Gerbracht U, Zenk G, Timmermann-Trosiener I, Bentley P, Waechter F, Schulte-Hermann R (1986) Pyruvate kinase isoenzymes in altered foci and carcinoma of rat liver. Carcinogenesis 7:1351–1357
Sato K, Takaya S, Imai F, Hatayama I, Ito N (1978) Different deviation patterns of carbohydrate-metabolizing enzymes in primary rat hepatomas induced by different chemical carcinogens. Cancer Res 38:3086–3093
Sato K, Hatayama I, Hoshino K, Imai F (1981) Enzyme deviation patterns in primary rat hepatomas induced by sequential administration of two chemically different carcinogens. Cancer Res 41:4147–4153
Schapira F (1973) Isozymes and cancer. Adv Cancer Res 18:77–153
Schauer A, Kunze E (1968) Enzymhistochemische und autoradiographische Untersuchungen während der Cancerisierung der Rattenleber mit Diäthylnitrosamin. Z Krebsforsch 70:252–266
Sharma RM, Sharma C, Donnelly AJ Morris HP, Weinhouse S (1965) Glucose-ATP phosphotransferases during hepatocarcinogenesis. Cancer Res 25:193–199
Tatematsu M, Nagamine Y, Farber E (1983) Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver. Cancer Res 43:5049–5058
Wachstein M, Meisel E (1957) Histochemistry of hepatic phosphatases at a physiologic pH. Am J Clin Pathol 27:13–23
Zierz S, Katz N, Jungermann K (1983) Distribution of pyruvate kinase type L and M2 in microdissected periportal and perivenous rat liver tissue with different dietary states. Hoppe-Seylers Z Physiol Chem 364:1447–1453
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fischer, G., Ruschenburg, I., Eigenbrodt, E. et al. Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver. J Cancer Res Clin Oncol 113, 430–436 (1987). https://doi.org/10.1007/BF00390036
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00390036