Abstract
Phenobarbital (PB) is a well known tumor promoter, which in combination with an initiating drug is able to accelerate the development of γ-glutamyl-transferase (γ-GT)-positive foci and to induce tumor formation after long term feeding1–4. PB is also found to stimulate liver growth1,3,5. The hypolipidaemic drugs nafenopin and clofibrate induce liver tumors when fed to rats or mice6–9. They do not, however, stimulate growth of γ-GT-positive foci3,10,11. Recently we have shown some alterations in carbohydrate metabolizing enzymes in hepatocarcinomas induced with NNM and promoted by long term feeding with phenobarbital or clofibrate12. Pyruvate Kinase (PK) and fructose-1,6-biphosphatase (FBPase) activities were reduced and malic enzyme activity was increased in these rat liver tumors with and without PB or clofibrate feeding. The activity of γ-GT, however, was dependent on the applicated drugs since only PB induced γ-GT-positive hepatocarcinomas. In this study activities of some enzymes were recorded after short term feeding of PB, clofibrate (Clof) or nafenopin (Naf) for 6 and 16 weeks. The results were compared with data obtained from long term application of these compounds for 64 weeks. Pyruvate kinase isoenzyme type L (LPK), malic enzyme (ME) and γ-glutamyltransferase were also investigated by immunohistological and histochemical methods.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
R. Schulte-Hermann, Tumor promotion in the liver, Arch. Toxicol. 57:147 (1985).
M. A. Pereira, S. L. Herren-Freund, A. L. Britt and M. M. Khouny, Effect of coadministration of phenobarbital sodium on NNM-induced GGT-positive foci and hepatocellular carcinoma in rats, JNCI 72:741 (1983).
S. Numoto, K. Furukawa, K. Furuya and M. Williams, Effects of hepatocarcinogenic peroxisome-proliferating hypolipidaemic agents Clofibrate and Nafenopin on the rat liver cell membrane enzymes γ-GT and alkaline phosphatase and on the early stages of liver carcinogenesis, Carcinogenesis 5:1603 (1984).
T. Kitagawa and H. Sugano, Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3′-Methyl-4-(dimethylamino)azobenzene or diethylnitrosamine, Gann 69:679 (1978).
R. Schulte-Hermann, Induction of liver growth by xenobiotic compounds and other stimuli, Crit. Rev. Toxicol. 3:97 (1974).
J. K. Reddy and N. D. Lalwai, Carcinogenesis by hepatic peroxisome proliferators: Evaluation of the risk of hypolipidaemic drugs and industrial plasticizers to humans, Crit. Rev. Toxicol. 12:1 (1983).
J. M. Reddy and M. S. Rao, Malignant tumors in rats fed nafenopin, a hepatic peroxisome proliferator, J. Natl. Cancer Inst. 59:1645 (1977).
J. K. Reddy and S. A. Qureshi, Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-α-p-chlorophenoxyisobutyrate (clofibrate) in rats, Br. J. Cancer 40:476 (1979).
Y. Mochizuki, K. Furukawa and N. Sawada, Effects of simultaneous administration of clofibrate with diethylnitrosamine on hepatic tumorigenesis in the rat, Cancer Letters 19:99 (1983).
W. Staubli, P. Bentley, F. Bieri, E. Frohlich and F. Waechter, Inhibitory effect of nafenopin upon the development of DENA-induced enzyme-altered foci within the rat liver, Carcinogenesis 5:41 (1984).
U. Gerbracht, I. Timmermann-Trosiener and R. Schulte-Hermann, Studies on regression of foci after withdrawal of tumor promoters, Fd. Chem. Toxic. 23:881 (1985).
U. Gerbracht, E. Roth, K. Becker, M. Reinacher and E. Eigenbrodt, A study of the activities of carbohydrate metabolizing enzymes and the levels of carbohydrate metabolites and amino acids in normal liver and in hepatocellular carcinoma, in: “Experimental Hepatocarcinogenesis”, M. Roberfroid and V. Preat, eds., Plenum Press, New York, (1988).
A. M. Rutenburg, H. Kim, H. W. Fischbein, J. S. Hanker, H. L. Wasserkrug and A. M. Seligman, Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity, J. Histochem. Cytochem. 17:517 (1969).
Z. Lojda, R. Gossrau and T. H. Schiebler, “Enzyme Histochemistry: A Laboratory Method”, Springer-Verlag, Berlin, Heidelberg, New York (1979).
G. Fischer, M. Domingo, D. Lodder, N. Katz, M. Reinacher and E. Eigenbrodt, Immunohistochemical demonstration of decreased L-pyruvate kinase in enzyme altered rat liver lesions produced by different carcinogens, Virchows Arch. B 53:359 (1987).
E. Eigenbrodt and W. Schoner, Purification and properties of the pyruvate kinase isoenzymes type L and M from chicken liver, Hoppe-Seyler’s Z. Physiol. Chem. 358:1033 (1977).
A. McPherson, D. Burkey and P. Stankiewicz, Crystalline alkaline form fructose-1,6-dephosphatase, J. Biol. Chem., 252:7031 (1977).
M. Zelewski and J. Swierczynski, The effect of clofibrate feeding on the NADP-linked dehydrogenase activity in rat tissue, Biochim. Biophys. Acta 758:152 (1983).
G. W. Löhr and H. D. Waller, Glucose-6-phosphat-Dehydrogenase, in: “Methoden der enzymatischen Analyse”, H. Bergmeyer, ed., Verlag Chemie, Weinheim (1974).
U. Bergmeyer, K. Grawehn and M. Graßl, Enolase, in: “Methoden der Enzymatischen Analyse”, H. Bergmeyer, ed., Verlag Chemie, Weinheim, (1974).
U. Bergmeyer, K. Grawehn and M. Graßl, Lactat-Dehydrogenase, in: “Methoden der enzymatischen Analyse”, H. Bergmeyer, ed., Verlag Chemie, Weinheim (1974).
J. P. Persijn and W. Van der Silk, L-γ-Glutamyltransferase, J. Clin. Chem. Clin. Biochem. 14:421 (1976).
German Society for Clinical Chemistry, Alkaline “Optimierte Standard-Gesellschaft für Klinische Chemie (1976).
J. K. Reddy, M. S. Rao, D. L. Azarnoff and S. Sell, Mitogenic and carcinogenic effects of a hypolipidaemic peroxisome proliferator (Wy-14, 643) in rat and mouse liver, Cancer Res. 39:151 (1979).
M. S. Rao, N. D. Lalweni and J. K. Reddy, Sequential histologic study of rat liver during peroxisome proliferator [4-Chloro-6-(2, 3-xylidino)-2-pyrimidinyl-thio]-acetic acid (Wy-14, 643)-induced carcinogenesis, J. Natl. Cancer Inst. 73:983 (1984).
A. B. Deangelo and C. T. Garret, Inhibition of development of praeneoplastic lesions in the livers of rats fed a weakly carcinogenic environmental contaminant, Cancer Letters 20:199 (1983).
M. S. Rao, N. D. Lalwani, D. S. Scarpelli and J. K. Reddy, The absence of GGT activity in putative praeneoplastic lesions and in hepatocellular carcinomas induced in rats by the hypolipidaemic methode” conforming to the recommendations of the Deutsche peroxisome proliferator Wy-14, 643, Carcinogenesis 3:1231 (1982).
M. Best and C. Duncan, Lipid effects of a phenolic ether (Su-13437) in the rat. Comparison with CPIB, Artherosclerosis 12:185 (1970).
M. Reinacher, E. Eigenbrodt, U. Gerbracht, G. Zenk, I. Timmermann-Trosiener, P. Bentley, F. Waechter and R. Schulte-Hermann, Pyruvate kinase isozymes in altered foci and carcinoma of rat liver, Carcinogenesis 7:1351 (1986).
G. M. Ledda-Columbano, A. Columbano, S. Dessi, P. Coni, C. Chiodino and P. Pani, Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules, Carcinogenesis 6:1371 (1985).
M. A. Moore, H. Tsuda and N. Ito, Dehydrogenase histochemistry of N-ethyl-N-hydroxyethylnitrosamine-induced focal liver lesions in the rat increase in NADPH-generating capacity, Carcinogenesis 7:339 (1986).
D. Mayer, M. Moore and P. Bannasch, Biochemical correlation of glycogen content and activity of some enzymes of carbohydrate metabolism in rat liver during early stages of carcinogenesis, J. Cancer Res. Clin. Oncol. 104:99 (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gerbracht, U., Weiße, G., Schlatterer, B., Reinacher, M., Schulte-Hermann, R., Eigenbrodt, E. (1988). Comparative Study on the Effect of Different Treatment Schedules on Some Carbohydrate Metabolizing Enzyme Activities in Rats During Hepatocarcinogenesis. In: Feo, F., Pani, P., Columbano, A., Garcea, R. (eds) Chemical Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9640-7_38
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9640-7_38
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9642-1
Online ISBN: 978-1-4757-9640-7
eBook Packages: Springer Book Archive