Spectrum of Complex DNA Damages Depends on the Incident Radiation

Abstract Hada, M. and Sutherland, B. M. Spectrum of Complex DNA Damages Depends on the Incident Radiation. Radiat. Res. 165, 223–230 (2006). Ionizing radiation induces bistranded clustered damages— two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although induction of single-strand breaks (SSBs) and isolated lesions has been studied extensively, little is known about the factors affecting induction of clusters other than DSBs. To determine whether the type of incident radiation could affect the yields or spectra of specific clusters, we irradiated genomic T7 DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970 MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586 MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis, electronic imaging and number average length analysis. The yields (damages/Mbp Gy−1) of all damages decreased with increasing linear energy transfer (LET) of the radiation. The relative frequencies of DSBs compared to abasic and oxybase clusters were higher for the charged particles—including the high-energy, low-LET protons—than for the ionizing photons.

[1]  H. Paretzke,et al.  Calculated DNA double-strand break and fragmentation yields after irradiation with He ions , 2005 .

[2]  F A Cucinotta,et al.  Model for Radial Dependence of Frequency Distributions for Energy Imparted in Nanometer Volumes from HZE Particles , 2000, Radiation research.

[3]  H. J. Brede,et al.  Induction of DNA double-strand breaks by 1H and 4He lons in primary human skin fibroblasts in the LET range of 8 to 124 keV/microm. , 1999, Radiation research.

[4]  R. Cunningham,et al.  New substrates for old enzymes. 5-Hydroxy-2'-deoxycytidine and 5-hydroxy-2'-deoxyuridine are substrates for Escherichia coli endonuclease III and formamidopyrimidine DNA N-glycosylase, while 5-hydroxy-2'-deoxyuridine is a substrate for uracil DNA N-glycosylase. , 1994, The Journal of biological chemistry.

[5]  B M Sutherland,et al.  Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Sutherland,et al.  Electronic imaging system for direct and rapid quantitation of fluorescence from electrophoretic gels: application to ethidium bromide-stained DNA. , 1987, Analytical biochemistry.

[7]  E. Gajewski,et al.  Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. , 1992, Biochemistry.

[8]  G. Kraft,et al.  The formation of strand breaks in DNA after high-LET irradiation: a comparison of data from in vitro and cellular systems. , 1990, International journal of radiation biology.

[9]  P. Guida,et al.  Low levels of endogenous oxidative damage cluster levels in unirradiated viral and human DNAs. , 2003, Free radical biology & medicine.

[10]  J. Sutherland,et al.  Unidirectional pulsed-field electrophoresis of single- and double-stranded DNA in agarose gels: analytical expressions relating mobility and molecular length and their application in the measurement of strand breaks. , 1987, Analytical biochemistry.

[11]  S. Wallace,et al.  In vitro repair of synthetic ionizing radiation-induced multiply damaged DNA sites. , 1999, Journal of molecular biology.

[12]  J. Jay-Gerin,et al.  Monte Carlo Calculation of the Primary Radical and Molecular Yields of Liquid Water Radiolysis in the Linear Energy Transfer Range 0.3–6.5 keV/μm: Application to 137Cs Gamma Rays1 , 2001 .

[13]  Peter O'Neill,et al.  Efficiency of incision of an AP site within clustered DNA damage by the major human AP endonuclease. , 2002, Biochemistry.

[14]  B. Epe,et al.  Recognition of oxidized abasic sites by repair endonucleases. , 1994, Nucleic acids research.

[15]  K. Prise,et al.  A study of endonuclease III-sensitive sites in irradiated DNA: detection of alpha-particle-induced oxidative damage. , 1999, Carcinogenesis.

[16]  J. Ward,et al.  DNA strand-break yields after post-irradiation incubation with base excision repair endonucleases implicate hydroxyl radical pairs in double-strand break formation. , 2000, International journal of radiation biology.

[17]  S. Ljungquist.  A new endonuclease from Escherichia coli acting at apurinic sites in DNA. , 1977, The Journal of biological chemistry.

[18]  P O'Neill,et al.  Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events. , 1997, International journal of radiation biology.

[19]  S. Wallace,et al.  Alpha-deoxyadenosine, a major anoxic radiolysis product of adenine in DNA, is a substrate for Escherichia coli endonuclease IV. , 1994, Biochemistry.

[20]  K M Prise,et al.  A review of dsb induction data for varying quality radiations. , 1998, International journal of radiation biology.

[21]  Peter Jacob,et al.  Simulation of DNA Damage after Proton Irradiation , 2003, Radiation Research.

[22]  C. Limoli,et al.  DNA strand break yields after post-high LET irradiation incubation with endonuclease-III and evidence for hydroxyl radical clustering , 2001, International journal of radiation biology.

[23]  J. Sutherland,et al.  Quantifying DNA damage by gel electrophoresis, electronic imaging and number‐average length analysis , 2001, Electrophoresis.

[24]  B. Sutherland,et al.  Frequencies and relative levels of clustered damages in DNA exposed to gamma rays in radioquenching vs. nonradioquenching conditions , 2001, Environmental and molecular mutagenesis.

[25]  J. Kiefer,et al.  Heavy ion-induced DNA double-strand breaks in yeast. , 1992, International journal of radiation biology.

[26]  F. Lederer,et al.  Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic sites. , 1990, The Journal of biological chemistry.

[27]  B. Demple,et al.  Homogeneous Escherichia coli endonuclease IV. Characterization of an enzyme that recognizes oxidative damage in DNA. , 1988, The Journal of biological chemistry.

[28]  G. Taucher‐Scholz,et al.  Influence of radiation quality on the yield of DNA strand breaks in SV40 DNA irradiated in solution. , 1999, Radiation research.

[29]  David M. Wilson,et al.  Processing of bistranded abasic DNA clusters in gamma-irradiated human hematopoietic cells. , 2004, Nucleic acids research.

[30]  M. Weinfeld,et al.  Reactivity of Human Apurinic/Apyrimidinic Endonuclease andEscherichia coli Exonuclease III with Bistranded Abasic Sites in DNA* , 1997, The Journal of Biological Chemistry.

[31]  J. Cadet,et al.  Formation of Modified DNA Bases in Cells Exposed either to Gamma Radiation or to High-LET Particles1 , 2002, Radiation research.

[32]  T. Nose,et al.  ESR Spin Trapping of Hydroxyl Radicals in Aqueous Solution Irradiated with High-LET Carbon-Ion Beams , 2003, Radiation research.

[33]  M. Takeshita,et al.  Interactions of Escherichia coli endonuclease IV and exonuclease III with abasic sites in DNA. , 1994, The Journal of biological chemistry.

[34]  M. Saparbaev,et al.  The ring fragmentation product of thymidine C5-hydrate when present in DNA is repaired by the Escherichia coli Fpg and Nth proteins. , 1998, Biochemistry.

[35]  M. Chung,et al.  8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Saparbaev,et al.  Alternative nucleotide incision repair pathway for oxidative DNA damage , 2002, Nature.