Reductive Damage in Directly Ionized DNA: Saturation of the C5 = C6 Bond of Cytosine in d(CGCG)<sub>2</sub>Crystals

Debije, Michael G.; Close, David M.; Bernhard, William A.

doi:10.1667/0033-7587(2002)157[0235:rdidid]2.0.co;2

Cited by 18 publications

(19 citation statements)

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“…This radical was formed at 4K and the dose response was linear at low dose, indicating that it is formed by single-track chemistry. 48,49 The formation of Cyt(C6+H, N3+H) •+ is thus explained by Reactions 6.1a , 6.1b , and 6.1c . If Cyt(C6+H, N3+H) •+ captures an electron, Reaction 6.3a , 3,6-diHCyt forms.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

2011

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It has been generally assumed that product formation in DNA damaged by ionizing radiation is relatively independent of base sequence; i.e., that the yield of a given product depends primarily on the chemical properties of each DNA constituent and not on its base sequence context. We examined this assumption by comparing direct-type end products produced in films of d(CTCTCGAGAG)2 with those produced in films of d(GCACGCGTGC)2. Here we report the product yields in d(CTCTCGAGAG)2 hydrated to Γ = 2.5 and 15, where Γ is the hydration level given in mol H2O/mol nucleotide. Of the 16 products monitored by GC/MS, 7 exhibited statistically significant yields: 8-oxoGua, 8-oxoAde, 5-OHMeUra, 5,6-diHUra, 5,6-diHThy, 5-OHCyt, and 5-OHUra. These yields at Γ = 2.5 are compared with the yields from our previously reported study of d(GCACGCGTGC)2 (after projecting the yields to a CG/AT ratio of 1). The ratio of projected yields, d(CTCTCGAGAG)2 divided by d(GCACGCGTGC)2, are 1.3 ± 0.9, 1.8 ± 0.3, 1.6 ± 0.6, 11.4 ± 4.7, 0.2 ± 0.1, > 28, and 0.8 ± 1.1, respectively. Considering just d(CTCTCGAGAG)2, the ratio of yields at Γ = 2.5 divided by yields at Γ = 15, are 0.7 ± 0.2, 0.5 ± 0.1, 2.3 ± 4.0, 3.4 ± 1.2, 3.5 ± 3.3, 1.2 ± 0.2, and 0.4 ± 0.2, respectively. The effects of sequence and hydration on base product yields are explained by a working model emphasizing the difference between two distinctly different types of reaction: i) radical reactions that progress to non-radical intermediates and product prior to dissolution and ii) reactions that stem from radicals trapped in the solid state at room temperature that go on to yield non-radical product after sample dissolution. Based on these findings, insights into rates of hole and excess electron transfer relative to rates of proton transfer are discussed.

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Section: Discussionmentioning

confidence: 99%

“…48,49 Therefore, some fraction of this radical may persist until the DNA is dissolved. That fraction would react with O 2 to give the peroxyl radical (Reaction 6.5a ), which would abstract hydrogen (Reaction 6.5b ).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

2011

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“…The two major products stemming from reduction of DNA are DHUra and DHThy. DHUra formation is initiated by the capture of an electron by cytosine, which subsequently protonates at either C5 or C6 (reaction 11) (28,29) and upon a second one-electron reduction results in dihydrocytosine (reaction 12). DHCyt in water deaminates via reaction (13) to give DHUra.…”

Section: Introductionmentioning

confidence: 99%

On the Chemical Yield of Base Lesions, Strand Breaks, and Clustered Damage Generated in Plasmid DNA by the Direct Effect of X Rays

2007

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The purpose of this study was to determine the yield of DNA base damages, deoxyribose damage, and clustered lesions due to the direct effects of ionizing radiation and to compare these with the yield of DNA trapped radicals measured previously in the same pUC18 plasmid. The plasmids were prepared as films hydrated in the range 2.5 < Γ < 22.5 mol water/mol nucleotide. Single-strand breaks (SSBs) and double-strand breaks (DSBs) were detected by agarose gel electrophoresis. Specific types of base lesions were converted into SSBs and DSBs using the base-excision repair enzymes endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The yield of base damage detected by this method displayed a strikingly different dependence on the level of hydration (Γ) compared with that for the yield of DNA trapped radicals; the former decreased by 3.2 times as Γ was varied from 2.5 to 22.5 and the later increased by 2.4 times over the same range. To explain this divergence, we propose that SSB yields produced in plasmid DNA by the direct effect cannot be analyzed properly with a Poisson process that assumes an average of one strand break per plasmid and neglects the possibility of a single track producing multiple SSBs within a plasmid. The yields of DSBs, on the other hand, are consistent with changes in free radical trapping as a function of hydration. Consequently, the composition of these clusters could be quantified. Deoxyribose damage on each of the two opposing strands occurs with a yield of 3.5 ± 0.5 nmol/J for fully hydrated pUC18, comparable to the yield of 4.1 ± 0.9 nmol/J for DSBs derived from opposed damages in which at least one of the sites is a damaged base.

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“…EPR spectroscopy has proven to be a successful method for studying the nature of free radicals formed in DNA and related constituents in the solid state (8)(9)(10)(11)(12). The bases of the DNA helix are important targets for the primary action of ionizing radiation, with the pyrimidine bases, thymine and cytosine, being the most probable reduction sites (13).…”

Section: Introductionmentioning

confidence: 99%

Radical Formation in Pyrimidine Bases after X, Proton and α-Particle Irradiation

Malinen

Sagstuen

2003

Radiation Research

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Single crystals of anhydrous thymine (Ta) and cytosine monohydrate (Cm) were irradiated at room temperature using X rays, 20 MeV protons and 35 MeV alpha particles, and the relative distributions of the various radiation-induced stable radicals in the crystals were investigated. These two crystal systems were chosen because of systematic differences in their molecular packing and hydrogen-bonding network. The radicals stabilized in these systems have previously been identified and analyzed by several authors. Experimental EPR spectra could thus be reconstructed based on simulated benchmark spectra using a fitting procedure, yielding the relative amounts of the different radical species. It was found that the relative amounts of a given radical species varied with the type of radiation used, with differences being most prominent between alpha particles and protons or X rays. In Ta, an increased production of hydrogen addition or abstraction radicals was found after exposure to alpha particles. These radicals are believed to be formed predominantly from superexcited states, resulting from the higher density of ionizations along the track of the alpha particle. A corresponding reduction in radicals derived from proton transfer reactions was observed in comparison with exposure to protons or X rays. In Cm, the differences were smaller than for Ta. This is probably due to differences in the arrangement of the crystal lattice between the two systems, with Cm having an extended hydrogen-bonding network promoting fast proton transfers after ionization. Most interesting, however, was the observation that more than 50% of the radical population in Cm not could be accounted for by known radical species. The population with an unknown origin was represented with a broad singlet, having a line width of 1.5 mT and a g value of 2.0045, in the spectral reconstruction procedure.

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Reductive Damage in Directly Ionized DNA: Saturation of the C5 = C6 Bond of Cytosine in d(CGCG)₂Crystals

Cited by 18 publications

References 58 publications

Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

On the Chemical Yield of Base Lesions, Strand Breaks, and Clustered Damage Generated in Plasmid DNA by the Direct Effect of X Rays

Radical Formation in Pyrimidine Bases after X, Proton and α-Particle Irradiation

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Reductive Damage in Directly Ionized DNA: Saturation of the C5 = C6 Bond of Cytosine in d(CGCG)2Crystals

Cited by 18 publications

References 58 publications

Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products

On the Chemical Yield of Base Lesions, Strand Breaks, and Clustered Damage Generated in Plasmid DNA by the Direct Effect of X Rays

Radical Formation in Pyrimidine Bases after X, Proton and α-Particle Irradiation

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Reductive Damage in Directly Ionized DNA: Saturation of the C5 = C6 Bond of Cytosine in d(CGCG)₂Crystals