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Expression of a Novel N-Acetylglucosaminyltransferase in Rat Hepatic Nodules

  • Rosa Pascale
  • Saroja Narasimhan
  • Srinivasan Rajalakshmi

Abstract

The hallmark of liver cancer research in recent years has been the development of experimental models by which initiation, promotion and progression phases can be studied1–4. Even though several agents act as promoters, yet many of them are organ specific. Nonetheless, promotion by orotic acid is elegant in that by selecting the initiating carcinogen both cancer in the liver5,6 as well as intestine7 can be achieved. Being an intermediate in the de novo biosynthesis of pyrimidine nucleotides, orotic acid is rapidly metabolized by the liver to uridine nucleotides, which on accumulation creates an imbalance in the pool sizes of nucleotides. Interestingly, promotion by orotic acid can be reversed either by blocking the conversion of orotic acid into uridine nucleotides or by trapping the accumulated uridine nucleotides8. These observations suggest that the pool sizes of nucleotides may have an important role in the promotion phase of the carcinogenic process. An understanding of the metabolic principles underlying orotic acid induced tumor promotion therefore requires a study on the effect of an imbalance of nucleotides on macromolecular biogenesis involving a template process such as nucleic acid synthesis or a non-template process like glycosylation. Glycosylation being a non-template process is regulated by a number of factors including the level and availability of nucleotide sugars.

Keywords

Orotic Acid Hepatic Nodule Baby Hamster Kidney Cell Glycoprotein Synthesis Uridine Nucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    C. Peraino, R. J. M. Fry and E. F. Staffeldt, Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene, Cancer Res. 48:1506 (1971).Google Scholar
  2. 2.
    D. B. Solt and E. Farber, New Principle for the analysis of chemical carcinogenesis, Nature (Lond) 263:702 (1976).CrossRefGoogle Scholar
  3. 3.
    H. C. Pitot, L. Barsness, T. Goldsworthy and T. Kitagawa, Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine, Nature (Lond) 271:456 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    D. S. R. Sarma, P. M. Rao and S. Rajalakshmi, Liver tumor promotion by chemicals: Models and mechanisms, Cancer Surveys 5:781 (1986).PubMedGoogle Scholar
  5. 5.
    C. Laurier, M. Tatematsu, P. M. Rao, S. Rajalakshmi and D. S. R. Sarma, Promotion by orotic acid of liver carcinogenesis in rats initiated by 1,2-dimethylhydrazine, Cancer Res. 44:2186 (1984).PubMedGoogle Scholar
  6. 6.
    P. M. Rao, Y. Nagamine, M. W. Roomi, S. Rajalakshmi and D. S. R. Sarma, Orotic acid, a new promoter for liver carcinogenesis, Toxicologic. Path. 12:173 (1984).CrossRefGoogle Scholar
  7. 7.
    P. M. Rao, E. Laconi, S. Rajalakshmi and D. S. R. Sarma, Orotic acid, a liver tumor promoter, also promotes carcinogenesis of the intestine, Proc. Amer. Assoc. Cancer Res. 27:142 (1986).Google Scholar
  8. 8.
    P. M. Rao, E. Laconi, S. Vasudevan, A. Denda, S. Rajagopal, S. Rajalakshmi and D. S. R. Sarma, Dietary and metabolic manipulations of the carcinogenic process: Role of nucleotide pool imbalances in carcinogenesis, Toxicologic. Path. 15:190 (1987).CrossRefGoogle Scholar
  9. 9.
    R. Kornfeld and S. Kornfeld, Assembly of asparagine-linked oligosaccharides, Ann. Rev. Biochem. 54:631 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Schachter, Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides, Biochem. Cell. Biol. 64:163 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    J. C. Collard, P. Van Beek, J. W. G. Jansen and J. F. Schijven, Transfection by human oncogenes: concomitant induction of tumorigenicity and tumor associated membrane alterations, Int. J. Cancer 35:207 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    U. V. Santer, F. Gilbert and M. C. Glick, Change in glycosylation of membrane glycoproteins after transfection on NIH 3T3 with human tumor DNA, Cancer Res. 44:3730 (1984).PubMedGoogle Scholar
  13. 13.
    M. Pierce and J. Arango, Rous sarcoma virus-transformed baby hamster kidney cells expresses higher levels of asparagine-linked tri-and tetraantenary glycopeptides containing [GlcNAc-γ(1,6) Man-α(1,6)-Man] and poly-N-acetyllactosamine sequences than baby hamster kidney cells, J. Biol. Chem. 261:10771 (1986).Google Scholar
  14. 14.
    J. W. Dennis, S. Laferte, C. Waghorne, M. L. Breitman and R. S. Kerbel, ß1–6 branching of Asn-linked oligosaccharides is directly associated with metastasis, Science 236:582 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    K. Yamashita, A. Hitoi, N. Taniguchi, N. Yokosawa, T. Yutaka and A. Kobata, Comparative study of the sugar chains of γ-glutamyltranspeptidases purified from rat liver and rat-AH-66 hepatoma cells, Cancer Res. 43:5059 (1983).PubMedGoogle Scholar
  16. 16.
    N. Yamaguchi, K. Kawai and T. Ashihara, Discrimination of γ-glutamyltranspeptidase from normal and carcinomatous pancreas, Clinica Chimica Acta 154:133 (1986).CrossRefGoogle Scholar
  17. 17.
    S. Narasimhan, N. Harpaz, G. Longmore, J. P. Carver, A. A. Grey and H. Schachter, Control of glycoprotein synthesis. The purification by preparative high voltage paper electrophoresis in borate of glycopeptides containing high mannose and complex oligosaccharide chains linked to asparagine, J. Biol. Chem. 255:4876 (1980).PubMedGoogle Scholar
  18. 18.
    S. Narasimhan, J. R. Wilson, E. Martin and H. Schachter, A structural basis for four distinct elution profiles on con A-sepharose affinity chromatography of glycopeptidases, Can. J. Biochem. 57:83 (1979).PubMedGoogle Scholar
  19. 19.
    S. Narasimhan, Control of glycoprotein synthesis. UDP-GlcNAc: glycopeptide ß4-N-acetylglucosaminyltransferase III. An enzyme in hen oviduct which adds GlcNAc in ß1–4 linkage to the ß linked mannose of trimannosyl core of N-glycosyl oligosaccharides, J. Biol. Chem. 257:10235 (1982).PubMedGoogle Scholar
  20. 20.
    S. Narasimhan, J. C. Freed and H. Schachter, Control of glycoprotein synthesis. Bovine milk UDP-galactose: N-acetylglucosamine ß-4 galactosyltransferase catalyses the preferential transfer of galactose to the GlcNAc ß1,2 Mana 1,3-branch of both bisected and non-bisected complex biantennary asparagine-linked oligosaccharides, Biochemistry 24:1694 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Narasimhan, J. C. Freed and H. Schachter, The effect of a “bisecting” N-acetylglucosaminyl group on the binding of biantennary, complex oligosaccharides to concanavalin A, Phaseolus vulgaris erythro-agglutinin [E-PHA] and Ricinus communis agglutinin (RCA-120) immobilised on agarose, Carbohydrate Res. 149:65 (1986).CrossRefGoogle Scholar
  22. 22.
    M. A. Sells, S. L. Katyal, S. Sell, H. Shinozuka and B. Lombardi, Induction of foci of altered γ-glutamyltranspeptidase positive hepatocytes in carcinogen-treated rats fed a choline-deficient diet, Br. J. Cancer 20:274 (1979).CrossRefGoogle Scholar
  23. 23.
    A. Kobata, The carbohydrates of glycoproteins, in: “Biology of Carbohydrates”, V. Ginsberg and P. W. Robbins, eds., John Wiley and Sons, Vol. 2 (1984).Google Scholar
  24. 24.
    C. Campbell and P. Stanley, A dominant mutation to ricin resistance in Chinese hamster ovary cells induces UDP-GlcNAc: glycopeptide ß-4N-acetylglucosaminyltransferase III activity, J. Biol. Chem. 259:13370 (1984).PubMedGoogle Scholar
  25. 25.
    E. Laconi, S. Vasudevan, P. M. Rao, S. Rajalakshmi and D. S. R. Sarma, Hepatic nodules have a characteristic pattern of nucleotide pools distinct from that of the surrounding liver, Proc. Amer. Assoc. Cancer Res. 28:169 (1987).Google Scholar
  26. 26.
    J. R. Brisson and J. P. Carver, Solution conformation of asparaginelinked oligosaccharides: α(1–2)-, α1–3-, ß(1–2)-, and ß1–4 linked units, Biochemistry 22:3671 (1983).PubMedCrossRefGoogle Scholar
  27. 27.
    J. R. Brisson and J. P. Carver, Solution conformation of asparaginelinked oligosaccharides: (1–6)linked moiety, Biochemistry 22:3680 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    B. D. Shur, E. M. Bayna, R. B. Runyan, J. S. Reichner, D. M. Scully and E. Kurt-Jones, The receptor function of cell surface glycosyl-transferases during mammalian fertilisation, development and immune recognition, in: “Colloque INSERUM/CNRS, Cellular and Pathological Aspects of Glycoconjugate Metabolism”, H. Dreyfus, R. Manarelli, L. Freysz, and G. Rebel, eds., Paris (1984).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Rosa Pascale
    • 1
  • Saroja Narasimhan
    • 2
  • Srinivasan Rajalakshmi
    • 1
  1. 1.Department of Pathology, Medical Sciences BuildingUniversity of TorontoTorontoCanada
  2. 2.Department of BiochemistryThe Hospital for Sick ChildrenTorontoCanada

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