ADP-ribose Polymer Metabolism: Implications for Human Nutrition

  • Elaine L. Jacobson
  • Viyada Nunbhakdi-Craig
  • Debra G. Smith
  • Hai-Ying Chen
  • Bryan L. Wasson
  • Myron K. Jacobson


Research which has led to our current understanding of the relationship between niacin and human health can be segregated into three distinct periods (Figure 1). The first period was concerned with the study of the killer disease, pellagra, and culminated with the discovery by Elvehjem and coworkers of nicotinate and nicotinamide as anti-pellagra factors (1). The second period led to the understanding that nicotinate and nicotinamide were converted within cells to NAD and NADP and that these pyridine nucleotides play a fundamental role in the hydride transfer reactions central to cellular energy metabolism. The third period involves the study of the involvement of NAD as the donor in ADP-ribose transfer reactions. While multiple classes of ADP-ribose transfer reactions occur in cells (2-4), the ADP-ribose metabolism of primary focus in the context described here is the utilization of NAD for the synthesis of polymers of ADP-ribose. As will be described below, the function of ADP-ribose polymer metabolism as a protective response of cells to carcinogen-induced DNA damage leads us to postulate that optimal niacin nutriture may be a preventive factor in carcinogenesis.


Nuclear Matrix Pyridine Nucleotide Hydride Transfer Reaction Dietary Niacin Enzymatic Cycling Assay 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Elvehjem, C. A., Madden, R. J., Strong, F. M., and Woolley, D. W., (1937) J. Am. Chem. Soc. 59, 1767.CrossRefGoogle Scholar
  2. 2.
    Jacobson, M. K. and Jacobson, E. L., Eds. ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. (1989) Springer-Verlag Publishers, Berlin, Heidelberg, New York.Google Scholar
  3. 3.
    Althaus, F.R. and Richter, C., Eds. ADP-Ribosylation of Proteins: Enzymology and Biological Significance. (1987) Springer-Verlag Publishers, Berlin, Heidelberg, New York.Google Scholar
  4. 4.
    Jacobson, M.K., Aboul-Ela, N., Cervantes-Laurean, D., Loflin, P.T. and Jacobson, E.L. ADP-Ribose Levels in Animal Cells. (1990) In ADPribosylating Toxins and G-Proteins: Insights into Signal Transduction, J. Moss and M. Vaughan, Eds., American Society for Microbiology, Washington, D.C., pp. 479–492.Google Scholar
  5. 5.
    Doll, R., and Peto, R. The Causes of Cancer,: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today. (1981) J. Natl. Cancer Institute 66, 1191–1308.Google Scholar
  6. 6.
    Ames, B.N., and Gold L. S. Dietary Carcinogens, Environmental Pollution, and Cancer: Some Misconceptions. (1990) Med. Oncol. Tumor Pharmacother. 7, 69–85.PubMedGoogle Scholar
  7. 7.
    Juarez-Salinas, H., Sims, J.L. and Jacobson, M.K. Poly(ADP-Ribose) Levels in Carcinogen Treated Cells, (1979) Nature 282, 740–741.PubMedCrossRefGoogle Scholar
  8. 8.
    Aboul-Ela, N., Jacobson, E.L. and Jacobson, M.K. Labeling Methods for the Study of Poly-and Mono(ADP-ribose) Metabolism in Cultured Cells. (1988) Analytical Biochemistry, 174, 239–250.PubMedCrossRefGoogle Scholar
  9. 9.
    Alvarez-Gonzalez, R., and Jacobson, M. K. Characterization of polymers of ADP-Ribose Generated Invitro and In vivo. (1987) Biochemistry 26, 3218–3224.PubMedCrossRefGoogle Scholar
  10. 10.
    Cardenas-Corona, M.E., Jacobson, E.L. and Jacobson, M.K. Endogenous Polymers of ADP-ribose are Associated with the Nuclear Matrix. (1987) Journal of Biological Chemistry 262, 14863–14866.PubMedGoogle Scholar
  11. 11.
    Nudka, N., Skidmore, C.J., and Shall, S. The Enhancement of Cytotoxicity of N-methyl-N-nitrosourea and of 7-Radiation by Inhibitors of Poly(ADP-Ribose) Polymerase. (1980) Eur. J. Biochem.,105, 525–530.CrossRefGoogle Scholar
  12. 12.
    Jacobson, E.L., Smith, J.Y., Mingmuang, M., Meadows, R., Sims, J.L. and Jacobson, M.K. Effect of Nicotinamide Analogues on Recovery from DNA Damage in C3H1OT1/2 Cells. (1984) Cancer Research 44, 2485–2492.PubMedGoogle Scholar
  13. 13.
    Jacobson, E.L., Smith, J.Y., Wielckens, K., Hilz, H. and Jacobson, M.K. Cellular Recovery of Dividing and Confluent C3H1OT1/2 Cells from Nmethyl-N-nitro-N-nitrosoguanidine in the Presence of ADP-Ribosylation Inhibitors. (1985) Carcinogenesis 6, 715–718.PubMedCrossRefGoogle Scholar
  14. 14.
    Jacobson, E.L., Smith, J.Y., Nunbhakdi, V. and Smith, D.G. ADP-Ribosylation Reactions in Biological Responses to DNA Damage. (1985) In ADPRibosylation of Proteins, F.R. Althaus, H. Hilz and S. Shall, Eds., Springer-Verlag, Berlin, Heidelberg, pp. 277–283.Google Scholar
  15. 15.
    Lubet, R.A., MacCarvill, J.T., Putman, D.L., Schwartz, J. L. and Schectman, K. M. Effect of 3-Aminobenzamide on the Induction of Toxicity And Transformation by Ethylmethane-Sulfonate and Methylcholanthrene in Balb/3T3 Cells. (1984) Carcinogenesis 5, 459–462.PubMedCrossRefGoogle Scholar
  16. 16.
    Takahasi, S., Nakae, D., Yokose, Y., Emi, Y., Denda, A., Mikami, T., Ohnishi, T., and Konishi, Y. Enhancement of DEN Initiation of Liver Carcinogenesis by Inhibitors of NAD+ADP-Ribose Transferase in Rats. (1984) Carcinogenesis 5, 901–906.CrossRefGoogle Scholar
  17. 17.
    Jacobson, E L, Lange, R.A. and Jacobson, M.K. Pyridine Nucleotide Synthesis in 3T3 Cells. (1979) Journal of Cellular Physiology 99, 417–426.PubMedCrossRefGoogle Scholar
  18. 18.
    Goldsmith, G. A., Sarett, H. P., Register, U. D., and Gibbens, J. Studies of Niacin Requirements in Man I. Experimental Pellagra in Subjects on Corn Diets Low in Niacin and Tryptophan. (1952) J. Clin. Invest. 31, 533–542.PubMedCrossRefGoogle Scholar
  19. 19.
    Goldsmith, G. A., Rosenthal, H. L., Gibbens, J., and Unglaub, G. Studies of Niacin Requirements in Man H. Requirements in Wheat and Corn Diets Low in Tryptophan. (1955) J. Nutr. 56, 371–386.PubMedGoogle Scholar
  20. 20.
    Goldsmith, G. A., Gibbens, J., Unglaub, G. and Miller, O. N. Studies of Niacin Requirements in Man Ill. Comparative Effects of Diets Containing Lime-treated and Untreated Corn in the Production of Experimental Pellagra. (1956) Am. J. Clin. Nutr, 4, 151–160.PubMedGoogle Scholar
  21. 21.
    Horwitt, M. K., Harvey, C C., Rothwell, W. S., Cutler, J. L., and Haffron, D. (1956) J. Nutr. 60 (Suppl. 1) 43.Google Scholar
  22. 22.
    Prates, M.D., and Torres, F.O. A cancer survey in Lourenco Marques, Portuguese East Africa. (1965) J. Natl. Cancer Inst., 35, 729–757.PubMedGoogle Scholar
  23. 23.
    Warwick, G.P. and Harrington, J.S. Some aspects of the epidemology and etiology of esophageal cancer with particular emphasis on the Transkei, South Africa. (1973) Adv. Cancer Res., 17, 81–229.CrossRefGoogle Scholar
  24. 24.
    Fu, C.S., Swendseid, M.E., Jacob, R.A. and McKee, R. W. Biochemical Markers for Assessment of Niacin Status in Young Men: Levels of Erythrocyte Niacin Coenzymes and Plasma Tryptophan. (1989) J. Nutr. 119, 1949–1955.PubMedGoogle Scholar
  25. 25.
    Jacobson, E.L. and Jacobson, M.K. Pyridine Nucleotide Levels as a Function of Growth in Normal and Transformed 3T3 Cells. (1976) Archives of Biochemistry and Biophysics 175, 627–634.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Elaine L. Jacobson
  • Viyada Nunbhakdi-Craig
  • Debra G. Smith
  • Hai-Ying Chen
  • Bryan L. Wasson
  • Myron K. Jacobson

There are no affiliations available

Personalised recommendations