5-Hydroxymethyl Uracil: A Product of Ionizing Radiation and Tritium Transmutation Formed in DNA

  • K. Frenkel
  • A. Cummings
  • G. W. Teebor
Part of the NATO ASI Series book series (NSSA, volume 124)


The mutagenic and carcinogenic properties of ionizing radiation are thought to be a consequence of DNA damage it causes (1). Such DNA damage includes single- and double-strand breaks, DNA-protein crosslinks, base loss with formation of AP sites and chemical modification of bases (2–6). Among the bases, the thymine moiety appears to be the most susceptible to the modifying effects of ionizing radiation (7, 8). One of the most studied derivatives formed through the action of ionizing radiation, thymine glycol (TG), is formed by the oxidation of the 5,6-double bond of thymine (Figure 1) (2, 9-13). TG is susceptible to further oxidation by radiogenically-derived hydroxyl radicals. It leads to the opening of the ring and formation of an unstable N’-formyl-N-pyruvyl urea (FPU) which either fragments or cyclizes and becomes 5-hydroxy-5-methyl hydantoin (HMH) (9, 10, 14). The other thymine derivative, 5-hydroxymethyl uracil (HMUra), is formed by oxidation of the methyl group of thymine (Figure 1) (15–17). In contrast to TG, HMUra is chemically stable (18). Therefore, it is possible that HMUra will serve as a marker of exposure to ionizing radiation in the same way as cyclobutane pyrimidine dimers became markers of exposure to UV radiation.


HeLa Cell Cyclobutane Pyrimidine Dimer Base Loss Control HeLa Cell Thymine Glycol 
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.



5-hydroxymethyl uracil




thymine glycol, 5,6-dihydroxy-5,6-dihydrothymine


thymidine glycol, 5,6-dihydroxy-5,6-dihydrothymidine


5-hydroxy-5-methyl hydantoin




high pressure liquid chromatography




single-stranded, ds, double-stranded

1 krad

10 Gy


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. Upton, in: “Cancer,” F. F. Becker, ed., Plenum Press, New York and London (1975), pp. 387–403.Google Scholar
  2. 2.
    P. A. Cerutti, in: “Photochemistry and Photobiology of Nucleic Acids, Vol. 2,” S. Y. Wang, ed., Academic Press, New York (19761976), pp. 375–401.Google Scholar
  3. 3.
    J. F. Ward and I. Kuo, Radiat. Res. 66:485–498 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    B. Dunlap and P. Cerutti, FEBS Lett. 51:188–190 (1975).PubMedCrossRefGoogle Scholar
  5. 5.
    G. Scholes, J. F. Ward, and J. Weiss, J. Mol. Biol. 2:379–391 (1960).PubMedCrossRefGoogle Scholar
  6. 6.
    H.-J. Rhaese and E. Freese, Biochim. Biophys. Acta 155:476–490 (1968).PubMedCrossRefGoogle Scholar
  7. 7.
    G. Scholes, in: “Photochemistry and Photobiology of Nucleic Acids, Vol. 1,” S. Y. Wang, ed., Academic Press, New York (1976), pp. 521–577.Google Scholar
  8. 8.
    J. Cadet and R. Teoule, Photochem. Photobiol. 28:661–667 (1978).PubMedCrossRefGoogle Scholar
  9. 9.
    R. Teoule, A. Bonicel, C. Bert, J. Cadet, and M. Polverelli, Radiat. Res. 57:46–58 (1974).PubMedCrossRefGoogle Scholar
  10. 10.
    R. Teoule, C. Bert, and A. Bonicel, Radiat. Res. 72:190–200 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    K. Frenkel, M. S. Goldstein, N. Duker, and G. W. Teebor, Biochemistry 20:750–754 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    K. Frenkel, M. S. Goldstein, and G. W. Teebor, Biochemistry 20:7566–7571 (1981).PubMedCrossRefGoogle Scholar
  13. 13.
    G. W. Teebor, K. Frenkel, and M. S. Goldstein, Prog. Mutat. Res. 4:301–311 (1982).Google Scholar
  14. 14.
    J. Cadet, M. Berger, and R. Teoule, Sov. J. Quantum Electron. 11:1576–1582 (1981).CrossRefGoogle Scholar
  15. 15.
    B. Ekert, Nature 194:278–279 (1962).PubMedCrossRefGoogle Scholar
  16. 16.
    L. S. Myers, Jr., J. F. Ward, W. T. Tsukamoto, D. E. Holmes, and J. R. Julca, Science 148:1234–1235 (1965).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Cadet and R. Teoule, Bull. Soc. Chim. Fr. 3-4:891–895 (1975).Google Scholar
  18. 18.
    R. E. Cline, R. M. Fink, and K. Fink, J. Am. Chem. Soc. 81:2521–2527 (1959).CrossRefGoogle Scholar
  19. 19.
    R. G. Kallen, M. Simon, and J. Marmur, J. Mol. Biol. 5:248–250 (1962).PubMedCrossRefGoogle Scholar
  20. 20.
    D. H. Roscoe and R. G. Tucker, Biochem. Biophys. Res. Commun. 16:106–110 (1964).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Okubo, B. Strauss, and M. Stodolsky, Virology 24:552–562 (1964).PubMedCrossRefGoogle Scholar
  22. 22.
    J. B. Meldrum, V. S. Gupta, and J. R. Saunders, Antimicrob. Ag. Chemother. 6:393–396 (1974).CrossRefGoogle Scholar
  23. 3.
    S. Waschke, J. Reefschlager, D. Barwolff, and P. Langen, Nature (London) 255:629–630 (1975).CrossRefGoogle Scholar
  24. 24.
    E. Matthes, D. Barwolff, B. Preussel, and P. Langen, in: “Antimetabolites in Biochemistry, Biology and Medicine,” J. Skoda and P. Langen, eds., Pergamon Press, Oxford (1978), pp. 115–126.Google Scholar
  25. 25.
    G. W. Teebor, K. Frenkel, and M. S. Goldstein, Proc. Natl. Acad. Sci. (USA) 81:318–321 (1984).CrossRefGoogle Scholar
  26. 26.
    K. Frenkel, A. Cummings, J. Solomon, J. Cadet, J. J. Steinberg, and G. W. Teebor, Biochemistry, 24:4527–4533 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    Z. M. Bacq and P. Alexander, in: “Fundamentals of Radiobiology,” Pergamon Press, Oxford, London, New York, Paris (1961), pp. 45–55.Google Scholar
  28. 28.
    L. E. Feinendegen and V. P. Bond, in: “Tritium,” A. A. Moghissi and M. W. Carter, eds., Messenger Graphix, Phoenix, AZ (1973), pp. 221-231.Google Scholar
  29. 29.
    S. Person, W. Snipes, and F. Krasin, Mutat. Res. 34:327–332 (1976).PubMedCrossRefGoogle Scholar
  30. 30.
    J. E. Cleaver, Genetics 87:129–138 (1977).PubMedGoogle Scholar
  31. 31.
    H. Licso, R. Baserga, and W. E. Kisieleski, Nature 192:571–572 (1961).CrossRefGoogle Scholar
  32. 32.
    D. J. Mewissen and J. H. Rust, in: “Tritium,” A. A. Moghissi and M. W. Carter, eds., Messenger Graphix, Phoenix, AZ (1973), pp. 252-267.Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • K. Frenkel
    • 1
  • A. Cummings
    • 1
  • G. W. Teebor
    • 1
  1. 1.Department of PathologyNew York University Medical CenterNew YorkUSA

Personalised recommendations