Radiation and Environmental Biophysics

, Volume 30, Issue 2, pp 71–79 | Cite as

DNA-radicals as structural monitors of direct radiation action: Sensitization by incorporation of 5-halouracils

  • J. Hüttermann


A survey over the development of studies and the present state of results concerning free radical formation in DNA by sparsely ionizing radiation as studied by electron spin resonance (ESR)-spectroscopy is presented. The emphasis is laid on solid state studies dealing with the determination of the chemical structure of radicals and of radical reactions rather than on quantitative aspects. As a system with close potential relation between model system studies and the in vivo response to radiation the question of radiosensitization of cells by incorporation of 5-halouracil derivatives into their DNA replacing thymine residues is discussed in some detail.


Free Radical Solid State Electron Spin Resonance System Study Present State 
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.
    Szybalski W (1974) X-ray sensitization by halopyrimidines. Cancer Chemother Rep (Part I) 58:539–557Google Scholar
  2. 2.
    Zimbrick ID, Ward JF, Myers Jr LS (1969) Studies on the chemical basis of cellular radiosensitization by 5-bromouracil substitution in DNA. II. Pulse and steady-state radiolysis of bromouracil-substituted and unsubstituted DNA. Int J Radiat Biol 16:525–534Google Scholar
  3. 3.
    Bonura T, Smith KC (1977) Sensitization ofE. coli to gamma-irradiation by 5-bromouracil incorporation. Int J Radiat Biol 32:457–469Google Scholar
  4. 4.
    Adams GE, Willson RL (1972) On the mechanism od BUdR sensitization a pulse radiolysis study of one electron transfer in nucleic acid derivatives. Int J Radiat Biol 22:589–597Google Scholar
  5. 5.
    Bansal KM, Patterson LK, Schuler RH (1972) The production of halide ion in the radiolysis of aqueous solutions of the 5-halouracils. J Phys Chem 76:2386–2392Google Scholar
  6. 6.
    Oloff H, Riederer H, Hüttermann J (1984) Free radical probes of condensed phase aspects of radiation damage mechanisms in DNA constituents: 5-halouracils. Ultramicroscopy 14:183–193Google Scholar
  7. 7.
    Riederer H, Hüttermann J, Symons MCR (1981) Matrix-isolation of free radicals from 5-halouracils II. Reactions of H in acidic glasses. J Phys Chem 85:2789–2797Google Scholar
  8. 8.
    Riederer H, Hüttermann J (1982) Matrix-isolation of free radicals from 5-halouracils. III Electron spin resonance of base oxidation in aqueous acidic glasses. J Phys Chem 86:3454–3463Google Scholar
  9. 9.
    Hüttermann J, Voit K, Oloff H, Köhnlein W, Gräslund A, Rupprecht A (1984) Specific formation of electron gain and electron loss centers in X-irradiated oriented fibers of DNA at low temperatures. Faraday Discuss Chem Soc 78:135–149Google Scholar
  10. 10.
    Zell I, Hüttermann J, Gräslund A, Rupprecht A, Köhnlein W (1989) Free radicals in irradiated oriented DNA-fibers: Results from B-form DNA and from deuterated DNA samples. Free Radic Res Comm 6:105–106Google Scholar
  11. 11.
    Zell I (1990) ESR-spectroskopische Untersuchungen freier Radikale in röntgenbestrahlten orientierten DNA-Fibern. PhD-Thesis, University of Saarland (FRG)Google Scholar
  12. 12.
    Shields H, Gordy W (1959) Electron spin resonance studies of radiation damage to nucleic acids and their constituents. Proc Natl Acad Sci (USA) 45:269–281Google Scholar
  13. 13.
    Boag J, Müller A (1959) Electron spin resonance in irradiated deoxyribonucleic acid. Nature 183:831–832Google Scholar
  14. 14.
    Ehrenberg A, Ehrenberg L, Löfroth G (1963) Thymidine-like electron-spin-resonance spectra in gamma-irradiated deoxyribonucleic acid. Nature 200:376–377Google Scholar
  15. 15.
    Gräslund A, Ehrenberg A, Rupprecht A, Ström G (1971) Ionic base radicals inγ-irradiated DNA. Biochim Biophys Acta 254:172–186Google Scholar
  16. 16.
    Herak JN, Gordy W (1965) Free radicals formed by hydrogen atom bombardment of the nucleic-acid bases. Proc Natl Acad Sci (USA) 54:1287–1292Google Scholar
  17. 17.
    Lenherr AD, Ormerod MG (1971) Electron reactions with thymidine inγ-irradiated frozen aqueous glasses. Proc R Soc London A 325:81–99Google Scholar
  18. 18.
    Gräslund A, Ehrenberg A, Rupprecht A, Tjälldin B, Ström G (1975) ESR kinetics of a free radical conversion inγ-irradiated oriented DNA. Radiat Res 61:488–503Google Scholar
  19. 19.
    Gregoli S, Olast M, Bertinchamps A (1974) Free radicals inγ-irradiated frozen solutions of deoxyadenosine-5′-monophosphate. A computer analysis of temperature-dependent ESR spectra. Radiat Res 60:388–404Google Scholar
  20. 20.
    Gregoli S, Olast M, Bertinchamps A (1979) Charge-migration phenomena inγ-irradiated costacking complexes of DNA nucleotides. II. An ESR study of various complexes in frozen solution. Radiat Res 77:417–431Google Scholar
  21. 21.
    Gregoli S, Olast M, Bertinchamps A (1982) Radiolytic pathways inγ-irradiated DNA: influence of chemical and conformational factors. Radiat Res 89:238–254Google Scholar
  22. 22.
    Gräslund A, Rupprecht A, Köhnlein W, Hüttermann J (1981) Radiation-induced free radicals in oriented bromouracil substituted DNA. Radiat Res 88:1–10Google Scholar
  23. 23.
    Riederer H, Hüttermann J, Symons MCR (1978)σ*-Electron addition to 5-halouracils in neutral glasses. Chem Comm 313–314Google Scholar
  24. 24.
    Voit K, Oloff H, Hüttermann J, Köhnlein W, Gräslund A, Rupprecht A (1986) Anionradicals from 5-halouracil substituted oriented DNA after X-irradiation at low temperatures. Radiat Environ Biophys 25:175–181Google Scholar
  25. 25.
    Bernhard WA (1981) Solid state radiation chemistry of DNA: the bases. Adv Radiat Biol 9:199–279Google Scholar
  26. 26.
    Hüttermann J (1982) Solid-state radiation chemistry of DNA and its constituents. Ultramicroscopy 10:25–40Google Scholar
  27. 27.
    Bernhard WA (1989) Sites of electron trapping in DNA as determined by ESR of one-electron-reduced oligonucleotides. J Phys Chem 93:2187–2189Google Scholar
  28. 28.
    Cullis PM, Podmore I, Lawson M, Symons MCR, Dalgarno B, McClymont J (1989) The site of electron capture in irradiated deoxyribonucleic acid: Cytosine vs. thymine. J Chem Soc Chem Comm 1003–1005Google Scholar
  29. 29.
    Hüttermann J, Voit K (1987) Free radicals from direct action of ionizing radiation in DNA: structural assignments from EPR spectroscopy. In: Weil J (ed) Electronic magnetic resonance of the solid state. The Canadian Society for Chemistry, Ottawa, pp 267–279Google Scholar
  30. 30.
    Rakvin B, Herak JN, Voit K, Hüttermann J (1987) Free radicals from single crystals of Deoxyguanosine-5′-monophosphate (Na-salt) irradiated at low temperatures. Radiat Environ Biophys 26:1–12Google Scholar
  31. 31.
    Hole EO, Nelson WH, Close DM, Sagstuen E (1987) ESR and ENDOR study of the guanine cation: Secondary product in 5′-dGMP. J Chem Phys 86:5218–5219Google Scholar
  32. 32.
    Voit K (1986) Molekulare Mechanismen der direkten Strahlenwirkung auf die DNS: ESR-spektroskopische Untersuchungen an röntgenbestrahlten, orientierten Fibern. PhD-Thesis, University of Regensburg (FRG)Google Scholar
  33. 33.
    Kaplan HS (1966) DNA-strand scission and loss of viability after X-irradiation of normal and sensitized bacterial cells. Proc Natl Acad Sci 55:1442–1446Google Scholar
  34. 34.
    Freifelder D, Freifelder DR (1966) Mechanism of X-ray sensitization of bacteriophage T7 by 5-bromouracil. Mutat Res 3:177–184Google Scholar
  35. 35.
    Lett JT, Caldwell I, Little JG (1970) Repair of X-ray damage to the DNA inMicrococcus radiodurans: the effect of 5-bromodeoxyuridine. J Mol Biol 48:395–108Google Scholar
  36. 36.
    Ling LL, Ward JF (1990) Radiosensitization of Chinese hamster V79 cells by bromodeoxyuridine substitution of thymidine: enhancement of radiation-induced toxicity and DNA strand break production by monofilar and bifilar substitution. Radiat Res 121:76–83Google Scholar
  37. 37.
    Tanooka H (1964) Direct and indirect inactivation of bacteriophage T6 containing halogenated DNA. Radiat Res 21:26–35Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • J. Hüttermann
    • 1
  1. 1.Fachrichtung Biophysik und Physikalische Grundlagen der MedizinUniversität des SaarlandesHomburg/SaarGermany

Personalised recommendations