Theoretical Modeling of Radiation‐Induced DNA Damage

Kumar, Anil; Sevilla, Michael D.

doi:10.1002/9780470526279.ch1

Cited by 33 publications

(67 citation statements)

References 173 publications

(298 reference statements)

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“…Simultaneously, theoretical calculations employing time-dependent density functional theory (TD-DFT) (Kumar and Sevilla, 2006, 2008, 2009) supported these experimental results. On this basis, ESR results shown in Figure 2 provide evidence for C3'• formation via photoexcitation of “pristine” 5-Me-2'-dC• + .…”

Section: Resultsmentioning

confidence: 65%

“…Thus, the identity and extent of various types of sugar radicals (e.g., C1′•, C3′•, and C5′•) produced via excited purine (guanine and adenine) (Adhikary et al 2005, 2008; Becker et al, 2007, 2010a, 2010b) and via pyrimidine (5-Me-2′-dC• + and of T(−H)• in Thd) cation radicals (this work) differ. Taking these results as well as the TD-DFT calculations into account (Adhikary et al 2005, 2008; Becker et al 2007, 2010a,b; Kumar et al 2008, 2009) and the results shown in Figure 8, it is suggested that the sites of high localization of spin and charge on the sugar moiety differ for excited purine and pyrimidine cation radicals and the sites of high spin and charge are those that lead to deprotonation and neutral radical formation.…”

Section: Discussionmentioning

confidence: 92%

“…The mechanism of sugar radical formation in the excited state of 5-Me-2′dC• + has been investigated following our previous works (Adhikary et al 2005, 2008; Becker et al 2007, 2010a,b; Kumar et al 2008, 2009) and employing the TD-B3LYP/6–31G(d) method. The thirty lowest vertical excited states were calculated for 5-Me-2′dC• + .…”

Section: Resultsmentioning

confidence: 99%

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Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Adhikary

Kumar

Palmer

et al. 2014

International Journal of Radiation Biology

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Purpose To study the formation and subsequent reactions of the 5-methyl-2′-deoxycytidine cation radical (5-Me-2′-dC•+) in nucleosides and DNA-oligomers and compare to one electron oxidized thymidine. Materials and methods Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2′-dC, thymidine (Thd) and their derivatives, in fully double stranded (ds) d[GC*GC*GC*GC*]2 and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG], where C* = 5-Me-C. Results We report 5-Me-2′-dC•+ production by one-electron oxidation of 5-Me-2′-dC by Cl2•− via annealing in the dark at 155 K. Progressive annealing of 5-Me-2′-dC•+ at 155 K produces the allylic radical (C-CH2•). However, photoexcitation of 5-Me-2′-dC•+ by 405 nm laser or by photoflood lamp leads to only C3′• formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5′-nucleotides leads to C3′• formation but not in 3′-TMP which resulted in the allylic radical (U-CH2•) and C5′• production. For excited 5-Me-2′,3′-ddC•+, absence of the 3′-OH group does not prevent C3′• formation. For d[GC*GC*GC*GC*]2 and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H)•:C(+H+)) is found with no observable 5-Me-2′-dC•+ formation. Photoexcitation of (G(N1-H)•:C(+H+)) in d[GC*GC*GC*GC*]2 produced only C1′• and not the expected photoproducts from 5-Me-2′-dC•+. However, photoexcitation of (G(N1-H)•:C(+H+)) in d[GGAC*AAGC:CCTAATCG] led to C5′• and C1′• formation. Conclusions C-CH2• formation from 5-Me-2′-dC•+ occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2′-dC•+ and 5-Me-2′,3′-ddC•+, spin and charge localization at C3′ followed by deprotonation leads to C3′• formation. Thus, deprotonation from C3′ in the excited cation radical is kinetically controlled and sugar C-H bond energies are not the only controlling factor in these deprotonations.

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Section: Resultsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 92%

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Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Adhikary

Kumar

Palmer

et al. 2014

International Journal of Radiation Biology

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“…Our present knowledge of LEE-DNA interactions derives essentially from theoretical calculations 4 and LEE impact experiments on gaseous DNA sub-units 3 and thin films of pure DNA held under ultra-high vacuum. 2 Although dry film experiments in vacuum were essential to unveil basic mechanisms of damage, they clearly do not correspond to cellular conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] It is now established that, for energies below 15 eV, LEEs localize on the DNA subunits to form transient negative ions (TNIs). [2][3][4] These latter can damage DNA by dissociating into a stable anion and one or more radical fragments (i.e., by dissociative electron attachment (DEA)) or by decaying into dissociative electronically excited states. 2,3 LEEs can also transfer from one DNA subunit to another, particularly from a base to the phosphate group, where they can induce cleavage of the C-O bond (i.e., break a DNA strand).…”

Section: Introductionmentioning

confidence: 99%

Low energy electron stimulated desorption from DNA films dosed with oxygen

Mirsaleh-Kohan

Bass

Cloutier

et al. 2012

The Journal of Chemical Physics

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Desorption of anions stimulated by 1-18 eV electron impact on self-assembled monolayer (SAM) films of single DNA strands is measured as a function of film temperature (50-250 K). The SAMs, composed of 10 nucleotides, are dosed with O 2 . The OH − desorption yields increase markedly with exposure to O 2 at 50 K and are further enhanced upon heating. In contrast, the desorption yields of O − , attributable to dissociative electron attachment to trapped O 2 molecules decrease with heating. Irradiation of the DNA films prior to the deposition of O 2 shows that this surprising increase in OH − desorption, at elevated temperatures, arises from the reaction of O 2 with damaged DNA sites. These results thus appear to be a manifestation of the so-called "oxygen fixation" effect, well known in radiobiology.

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Understanding DNA Radicals Employing Theory and Electron Spin Resonance Spectroscopy

Adhikary

Kumar

Becker

et al. 2012

Encyclopedia of Radicals in Chemistry, Biology and Materials

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Ionizing radiation, such as γ‐rays, X‐rays, or ion beam radiation, results in the formation of cation and anion radicals in DNA and neutral radicals by secondary reactions. These DNA radicals are stable at low temperatures and, therefore, can be studied by electron spin resonance (ESR) spectroscopy. In these DNA radicals, the unpaired spin on the radical site interacts with nuclei with a magnetic moment, such as, 1 H, 2 H, and 14 N. This electron spin–nuclear spin interaction gives rise to hyperfine coupling, which is characterized by the hyperfine coupling constant (HFCC) values. The HFCC values along with the g ‐values determine the ESR spectra of these radicals. Calculations based on density functional theory (DFT) allow for identification of these DNA radicals via the prediction of stabilization energies and, most importantly, accurate values of the HFCCs. These calculations elucidate radical conformational structures as well. Thus, the combination of ESR with DFT calculations is a powerful approach to the investigation of DNA radicals and is the main focus of this article. This is illustrated in this article by specific examples—such as the prediction of sites of deprotonation in the DNA base cation radicals, intra‐base pair proton transfer processes in DNA base radicals, and excited state‐induced reactions of the DNA base cation and anion radicals leading to sugar radical formation.

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Theoretical Modeling of Radiation‐Induced DNA Damage

Cited by 33 publications

References 173 publications

Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Reactions of 5-methylcytosine cation radicals in DNA and model systems: Thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar

Low energy electron stimulated desorption from DNA films dosed with oxygen

Understanding DNA Radicals Employing Theory and Electron Spin Resonance Spectroscopy

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