Decomposition of nucleoside hydroperoxide by metals and metalloproteins

  • Krystyna Frenkel
  • Soosan Tofigh
Section 5 Genetic Effects


5-Hydroperoxymethyl-2′-deoxyuridine (HPMdU) is formed in DNA by ionizing radiation. Although relatively stable, HPMdU eventually decomposes to two products 5-hydroxymethyl-2′-deoxyuridine (HMdU) and 5-formyl-2′-deoxyuridine (FdU). We show that a number of transition metal ions and metalloproteins accelerate this process. Of the metal ions tested, Sn(II) and Fe(II) were the most active, with the former producing exclusively HMdU, and the latter, a mixture of both. Cu(I), Cu(II), Co(II), and Ni(II) induced a predominant generation of FdU, with copper ions being more effective than Co and Ni. FdU was also preferentially formed in the presence of the iron-containing proteins transferrin and ferritin, whereas HMdU was the major product in the presence of apotransferrin as well as in the presence of ceruloplasmin, a copper-containing protein.

Index Entries

Thymidine hydroperoxide copper iron ceruloplasmin transferrin ferritin active oxygen species ionizing radiation oxidized DNA bases 


  1. 1.
    G. Scholes,Brit. J. Radiol. 56, 221 (1983).PubMedGoogle Scholar
  2. 2.
    R. Teoule and J. Cadet,Molecular Biology, Biochemistry and Biophysics, vol. 27, J. Hutterman, W. Kohnlein, R. Teoule, and A. J. Bertinchamps, eds., Springer, Berlin, 1978, pp. 171–203.Google Scholar
  3. 3.
    J. E. Frew, P. Jones, and G. Scholes,Mechanisms of DNA Damage and Repair, M. G. Simic, L. Grossman, and A. C. Upton, eds., Plenum, New York, 1986, pp. 61–67.Google Scholar
  4. 4.
    A. Upton,Cancer, F. F. Becker, ed., Plenum. New York and London, 1975, pp. 387–403.Google Scholar
  5. 5.
    A. W. Hsie, L. Recio, D. S. Katz, C. W. Lee, M. Wagner, and R. L. Schenley,Proc. Natl. Acad. Sci. USA 83, 9616 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Cadet, L. Voituriez, J. L. Seed, E. Bueding, T. Nagamatsu, and S. Y. Wang,International Round Table on Nucleotides, Nucleosides and Their Biological Applications, 4th, Antwerp, Belgium, 1981.Google Scholar
  7. 7.
    J. Cadet and R. Teoule,Bull. Soc. Chim. Fr. 3–4, 891 (1975).Google Scholar
  8. 8.
    S. Waschke, J. Reefschlager, D. Barwolff, and P. Langen,Nature (London.) 255, 629 (1975).CrossRefGoogle Scholar
  9. 9.
    J. B. Meldrum, V. S. Gupta, N. R. Lowes, and A. R. P. Paterson,Toxicol. Appl. Pharmacol. 79, 423 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    L. I. Kahilainen, D. E. Bergstrom, and J. A. Vilpo,Acta Chem. Scand. B. 39, 477 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    L. Shirnamé-Moré, T. G. Rossman, W. Troll, G. W. Teebor, and K. Frenkel,Mutation Res. 178, 177 (1987).PubMedGoogle Scholar
  12. 12.
    G. W. Teebor, K. Frenkel, and M. Goldstein,Proc. Natl. Acad. Sci. USA 81, 318 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    K. Frenkel, A. Cummings, J. Solomon, J. Cadet, J. J. Steinberg, and G. W. Teebor,Biochemistry 24, 4527 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    K. Frenkel, K. Chrzan, W. Troll, G. W. Teebor, and J. J. Steinberg,Cancer Res. 46, 5533 (1986).PubMedGoogle Scholar
  15. 15.
    K. Frenkel and K. Chrzan,Carcinogenesis 8, 455 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    K. Frenkel and K. Chrzan,Anticarcinogenesis and Radiation Protection, P. Cerutti, O. Nygaard, and M. Simic, eds., Plenum, New York, 1987, pp. 97–102.Google Scholar
  17. 17.
    S. Tofigh and K. Frenkel,Free Rad. Biol. Med., in press (1989).Google Scholar
  18. 18.
    S. D. Aust, L. A. Morehouse, and C. E. Thomas,J. Free Radicals Biol. Med. 1, 3 (1985).CrossRefGoogle Scholar
  19. 19.
    B. Halliwell and J. M. C. Gutteridge,Arch. Biochem. Biophys. 246, 501 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    M. Chevion,Free Rad. Biol. Med. 5, 27 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    R. R. Crichton and M. Charloteaux-Wauters,Eur. J. Biochem. 164, 485 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    K. Frenkel,Free Radical, Diseased States and Anti-radical Interventions, P. Beaumont, D. Deeble, B. Parsons, and C. Rice-Evans, eds., Richelieu, London, in press (1989).Google Scholar
  23. 23.
    P. Biemond, A. J. G. Swaak, H. G. van Eijk, and J. F. Koster,Free Rad. Biol. Med. 4, 185 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    J. M. McCord,Science (Wash., DC) 185, 529 (1974).CrossRefGoogle Scholar
  25. 25.
    S. P. Kunapuli, H. Singh, P. Singh, and A. Kumar,Life Sci. 40, 2225 (1987).PubMedCrossRefGoogle Scholar
  26. 26.
    K. H. Tan, D. J. Meyer, B. Coles, and B. Ketterer,FEBS Lett. 207, 231 (1986).PubMedCrossRefGoogle Scholar
  27. 27.
    B. Ketterer, K. H. Tan, D. J. Meyer, and B. Coles,Glutathione S-Transferases and Carcinogenesis, T. J. Mantle, C. Pickett, and J. Hayes, eds., Taylor and Francis, London, 1987, 149–163.Google Scholar

Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • Krystyna Frenkel
    • 1
  • Soosan Tofigh
    • 1
  1. 1.Department of Environmental MedicineNew York University Medical CenterNew York

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