Abstract
At doses at which mammalian cells are killed, ionizing radiation produces 3 × 103 — 3 × 104 altered moieties in the genomic DNA of the cell. Mechanisms whereby these alterations are produced are well described, i.e., from ’OH radicals, direct ionization of DNA (von Sonntag, 1987) and perhaps from peroxyl radicals arising from ’OH reactions with other cellular molecules (Ward et al., 1997). Enzymatic repair of altered bases is well documented, and since these altered bases are produced during endogenous oxidation it is not surprising that enzymatic processes have evolved for their removal (Lindahl,1990). Ionizing radiation also produces strand breaks, but it is not known if these are produced by endogenous oxidation. The repair of singly damaged sites is well known. However, ionizing radiation also produces multiply damaged sites (MDS): It deposits energy non-uniformly; increments of energy (average amount 60eV) in small (nanometer) volumes. Thus a resulting radical reacting with DNA frequently does so in the presence of other radicals which can also react in close proximity. MDS have three variables: 1. Types of lesions involved (base damage, strand break); 2. Total number of lesions involved (for low LET radiation the most frequent is two); 3. Size of the site over which the damages are distributed. MDS represent a challenge to the cellular repair systems, they represent sites in the DNA at which base identity has been destroyed on both strands; if the damaged sites are closely opposed there is no complimentary strand to guide repair.
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References
B.N. Ames, L.S. Gold and W.C. Willett (1995) The causes and prevention of cancer. Proc. Nat. Acad. Sci. (U.S.A.) 92, 5258–5265.
E.E. Budzinski, J.D. Dawidzik, J.C. Wallace, H.G. Freund and H.C. Box (1995) The radiation chemistry of d(CpGpTpA) in the presence of oxygen. Radiat. Res. 142, 107–109.
G.V. Buxton, C.L. Greenstock, W.P. Helman and A.B. Ross (1988) Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (OH/CT) in aqueous solution. J. Phys. Chem. Ref. Data 17, 513–886.
M.A. Chaudhry and M. Weinfeld (1995) The action of the Escherichia Coli endonuclease III on multiply damaged sites in DNA. J. Molec. Biol. 23, 914–922.
M.A. Chaudhry and M. Weinfeld (1997) Reactivity of human apurinic/apyrimidinic endonuclease and Escherichia Coli exonuclease III with bistranded abasic sites in DNA. J. Biol. Chem. 272, 15650–15655.
M. Dizdaroglu (1993) Quantitative determination of oxidative base damage in DNA by stable isotope-dilution mass spectrometry FEBS Lett. 315, 1–6.
T. Douki, T. Delatour, F. Bianchini and J. Cadet (1996) Observation and prevention of an artefactual formation of oxidized DNA bases and nucleosides in the GC-EIMS method. Carcinogenesis 17, 347–353.
M.M. Elkind and J.L. Redpath (1977) Molecular and cell biology of radiation lethality. In Cancer, A Comprehensive Treatise, Becker, F.F. editor Plenum Press 6, 51–99.
A.F. Fuciarelli, B.J. Wegher, W.F. Blakely and M. Dizdaroglu (1990) Yields of radiation-induced base products in DNA: effects of DNA conformation and gassing conditions. Int. J. Radiat. Biol. 58, 397–415.
E.J. Hall (1994) Radiobiology for the Radiologist. J.P. Lippincott, Philadelphia, PA.
B. Halliwell and M. Dizdaroglu (1992) The measurement of oxidative damage to DNA by HPLC and GC/MS techniques. Free Rad. Res. Commun. 16, 15–28.
J. Heilman, G. Taucher-Scholz, T. Haberer, M. Scholz and G. Kraft (1996) Measurement of intracellular DNA double-strand break induction and rejoining along the track of carbon and neon particle beams in water. Int J. Radial. Oncol. Biol. Phys. 34, 599–608.
W.D. Henner, L.O. Rodriguez, S.M. Hecht and W.A. Hazeltine (1973) γ-Ray induced deoxyribonucleic acid strand breaks. J. Biol. Chem. 258, 713–716.
C.D. Jonah and J.R. Miller (1977) Yield and decay of the OH radical from 200 ps to 3ns. J. Phvs. Chem. 81, 1974–1976.
M.V.M. Lafleur, J. Woldhuis and H. Loman (1979) Alkali-labile sites and post-irradiation effects in gamma-irradiated biologically active double-stranded DNA in aqueous solution. Int. J. Radiat Biol. 36, 241–247.
T. Lindahl, (1990) Repair of intrinsic DNA lesions. Mutat. Res. 238, 305–311.
M. Löbrich, B. Rydberg, and P. K. Cooper (1995) Repair of x-ray-induced DNA double strand breaks in specific Not I restriction fragments in human flbroblasts: Joining of correct and incorrect ends. Proc. Nat. Acad. Sci. (U.S.A.) 92, 12050–12054.
J.R. Milligan, J.A. Aguilera and J.F. Ward (1993) Variation of single strand break yield with scavenger concentration in plasmid DNA irradiated in aqueous solution. Radiat. Res. 133, 151–157.
J.R. Milligan, J.A. Aguilera, C.C.L. Wu, J.Y-Y. Ng and J.F. Ward (1996) The difference that LET makes to the precursors of DNA strand breaks. Radiat. Res. 145, 442–448.
J.R. Milligan, J.Y. Ng., C.C.L. Wu, J.A. Aguilera, J.F. Ward, Y.W. Kow, S.S. Wallace, and R.P. Cunningham (1996). Methyperoxyl radicals as intermediates in DNA damage by ionizing radiation. Radiat. Res. 146, 436–444.
T. Mori and M. Dizdaroglu (1994) Ionizing radiation causes greater DNA base damage in radiation-sensitive mutant MIO cells than in parent mouse lymphoma L5178Y cells. Radiat. Res. 140, 85–90.
T. Mori, Y. Hori and M. Dizdaroglu (1993) DNA base damage generated in vivo in hepatic chromatin of mice upon whole body γ-irradiation. Int. J. Radiat. Biol. 64, 645–650.
Z. Nackerdien, R. Olinski and M. Dizdaroglu (1992) DNA base damage in chromatin of irradiated cultured human cells. Free Radical Res. Commun. 16, 259–273
R. Roots and S. Okada (1972) Protection of DNA molecules of cultured mammalian cells from radiation-induced single strand scissions by various alcohols and SH compounds. Int. J. Radiat. Biol. 21, 329–342.
G. Scholes, J.F. Ward and J. Weiss (1960) Mechanisms of the radiation induced degradation of nucleic acids. J. Molec. Biol. 2, 379–381.
J.W.T. Spinks and R.J. Woods (1976) An Introduction to Radiation Chemistry (2nd Edition) John Wiley and Sons, New York.
S.G. Swarts, G.S. Smith, L. Miao and K.T. Wheeler (1996) Effects of formic acid hydrolysis on the quantitative analysis of radiation-induced DNA base damage products assayed by gas chromatography/mass spectrometry. Radiat. And Environ. Biophys. 35, 41–54.
C. von Sonntag (1987) The Chemical Basis of Radiation Biology, (Taylor and Francis, London)
J.F. Ward (1975) Molecular mechanisms of radiation induced damage to nucleic acids. Adv. Radiat. Biol. 5, 182–240.
J.F. Ward (1981) Some biochemical consequences of the spatial distribution of ionizing radiation produced free radicals. Radiat. Res. 86, 185–195.
J.F. Ward (1985) Biochemistry of DNA lesions. Radiat. Res. 104, S103–S111.
J.F. Ward (1988) DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation and repairability. Progress in Nucleic Acids and Molecular Biology, 35, 95–125.
J.F. Ward, C.L. Limoli and P.M. Calabro-Jones (1991) An examination of the repair saturation hypothesis for describing shouldered survival curves. Radiat. Res. 127, 90–96.
J.F. Ward, J.R. Milligan, and G.D.D. Jones (1994) Biological consequences of non-homogeneous energy depositions by ionizing radiation. Radiat. Protec. Dosim. 52, 271–276.
J.F. Ward, (1995) Radiation Mutagenesis: The initial DNA lesions responsible. Radiat. Res. 142, 362–368.
J.F. Ward and J.R. Milligan (1997) Four mechanisms for the production of complex damage. Radiat. Res. 148, 481–483.
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Ward, J.F. (1999). Ionizing Radiation Damage to DNA. In: Dizdaroglu, M., Karakaya, A.E. (eds) Advances in DNA Damage and Repair. NATO ASI Series, vol 302. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4865-2_35
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DOI: https://doi.org/10.1007/978-1-4615-4865-2_35
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