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530 Charged Particle and Photon Interactions with Matter

At ambient temperatures, photoinduced hole transfer in dsDNA oligomers in aqueous solution

has been reported to occur through long uninterrupted A tracts with little distance dependence

(Giese et al., 2001; Giese, 2002; Shao et al., 2004; Kawai and Majima, 2005; Joy et al., 2006;

Augustyn

et al., 2007; Lewis et al., 2008).

19.5.4 the protonation State of one-electron oxidized 2′-deoxyguanoSine

The DNA cation radicals G

•+

and A

•+

are well known to undergo transformation via two types of com-

petitive reactions: (1) reversible deprotonation reactions forming neutral radicals (G(-H)

•

and A(-H)

•

and (2) irreversible nucleophilic addition reaction of water (Steenken, 1989, 1992, 1997; Becker and

Sevilla, 1993, 1998, 2008; Bernhard and Close, 2004; Sevilla and Becker, 2004; von Sonntag, 2006;

Becker et al., 2007; Li and Sevilla, 2007; Close, 2008; Kumar and Sevilla, 2008a). The pK

of G

•+

dGuo in aqueous solution at ambient temperature has been found to be ca. 3.9 (Steenken, 1989, 1992,

1997); hence, at neutral pH, G

•+

in dGuo undergoes fast deprotonation to the surrounding water mol-

ecules (1.8 × 10

−1

) (Kobayashi and Tagawa, 2003). The slow hydration reaction at C-8 in G

•+

occurs

with the G

•+

in prototropic equilibrium with the dominant species G(-H)

•

Pulse radiolysis studies using optical detection and various analogs of dGuo had suggested that

deprotonation of G

•+

in dGuo could occur via loss of a proton from N1 to give G(N1-H)

•

(Scheme

19.9) (Steenken, 1989, 1992, 1997) and, at high pH > ca. 11, G(N1-H)

•

further deprotonates to pro-

duce G(-2H)

•−

(Scheme 19.9) with pK

= 10.8 (Steenken, 1989). These studies have shown that in

nucleotides of dGuo (e.g., in 5′-dGMP), the presence of the phosphate group did not signicantly

affect the prototropic equilibria shown in Scheme 19.9 (Steenken, 1989). Furthermore, the pK

of the

exocyclic amine group in 1-methylguanosine cation radical (1-Me-Guo

•+

) is found to be 4.7 at room

temperature (Steenken, 1989). This implies that, in dGuo, deprotonation from the exocyclic nitrogen

(N2) should be competitive with deprotonation from N1 (Scheme 19.9). Theoretical calculations

have shown that the energies involved in producing the N1 deprotonated G

•+

, that is, G(N1-H)

•

or the N2 deprotonated G

•+

, that is, G(N2-H)

•

, are very similar (Mundy et al., 2002; Luo et al.,

2005; Naumov and von Sonntag, 2008). Theoretical calculations had also suggested that G(N1-H)

•

would be favored over G(N2-H)

•

in environments with high dielectric constants, such as water (von

Sonntag,

2006; Naumov and von Sonntag, 2008).

–

G(N2-H)

(anti)

G(N1-H)

G(-2H)

–

= 10.8

–H

= 3.9

–H

G(N2-H)

(syn)

•

sCheme 19.9 The numbering scheme and prototropic equilibria of one-electron oxidized guanine cat-

ion radical (G

•+

), the mono-deprotonated species (G(N1-H)

•

and G(N2-H)

•

in syn and anti-conformers with

respect to the N3 atom), and the di-deprotonated species (G(-2H)

•−

). (Adapted from Adhikary, A. et al., J.

Phys. Chem. B,

110, 24171, 2006c.)

PhysicochemicalMechanisms of Radiation-Induced DNA Damage 531

ENDOR studies of x-ray-irradiated single crystals of Guo, dGuo, 5′-dGMP and 3′,5′-cyclic gua-

nosine monophosphate clearly show that in these crystalline environments, deprotonation of G

•+

results in G(N2-H)

•

rather than in G(N1-H)

•

(Bernhard and Close, 2004; Close, 2008) and refer-

ences

therein.

Thus,

even though a considerable number of experimental and theoretical studies had been

carried out on the deoxyguanosine cation radical (G

•+

) and its deprotonated species (G(-H)

•

), the

specic site of deprotonation (at N1 or at the exocyclic N-atom (N2)) was still not clear (Adhikary

et al., 2006c). However, in a recent ESR study of the prototropic equilibrium between G

•+

and

G(-H)

•

in dGuo, specic isotopic substitution of deuterium at C-8-H in the guanine ring and of

at N1, N2, and N3 atoms in the guanine ring, as well as, theoretical calculations (Adhikary etal.,

2006c) provided some insights to this issue.

Glassy homogenous aqueous (D

O) solutions of dGuo (2′-dG) in 7.5M LiCl were investigated

using ESR and UV–Vis spectroscopy in the pH range 3–12 (Adhikary et al., 2006c). In D

exchangeable hydrogen atoms (N1-H and two N2-H atoms) do not show observable hyperne cou-

pling (Adhikary et al., 2006c, 2008a, 2009). The three prototropic forms of one-electron-oxidized

guanine (G

•+

, G(-H)

•

, and G(-2H)

•−

) in dGuo (Scheme 19.9) were distinguished from each other in

the

pH ranges (3–5), (7–9), and (>11), respectively, and characterized.

Deuteration

of the C8 position in the guanine ring allowed the observation of the N

nitrogen

atom hyperne couplings at different states of the prototropic equilibria of G

•+

N isotropic substi-

tutions at N1, N2, and N3 in the guanine ring were used to verify these couplings and their assign-

ments to specic nitrogen atom sites. With knowledge of these couplings, ESR spectra simulations

allowed the determination of the C8(H) hyperne couplings in different protonation states of one-

electron oxidized guanine (Adhikary et al., 2006c) and gave strong evidence that the N1 site is the

site of deprotonation in G

•+

Ab initio DFT calculations for various one-electron oxidized guanine radicals with 7–10 waters

of hydration, conrmed assignments of experimentally observed hyperne couplings to nitrogen

atoms. A comparison of the calculated hyperne couplings of G(N1-H)

•

+ 7 H

O and G(N2-H)

•

7H

O with experimental values clearly conrm that the site of deprotonation in G

•+

is at N1 in

aqueous

solution (Adhikary et al., 2006c).

studies using pulse radiolysis with optical detection of 8-bromo-dGuo along with theo-

retical modeling (Chatgilialoglu et al., 2005, 2006) suggested that at rst, G

•+

in dGuo decays to

G(N2-H)

•

, which via subsequent water-assisted tautomerization is converted to G(N1-H)

•

. The work

described above (Adhikary et al., 2006c) suggests that with the inclusion of additional waters, G

•+

dGuo decays directly to G(N1-H)

•

19.5.5 the protonation State of one-electron oxidized guanine

in dsdna-oligoMerS: the role of baSe pairing

In dsDNA-oligomers or in DNA, the prototropic equilibrium of one-electron oxidized guanine,

Scheme 19.10, is controlled by two important proton transfer processes: (1) the intra-base proton

transfer process within the G

•+

:C base pair (Steenken, 1989, 1992, 1997; Becker and Sevilla, 1993,

N H

C(+H

)

C C

G(-H) G(N2-H)

N H

N H N

•

sCheme 19.10 Schematic representation of prototropic equilibria in the G

•+

:C pair. Both intra-base pair

proton transfer within the G

•+

:C base pair and proton transfer between the G

•+

:C base pair and surrounding

water

are shown.

532 Charged Particle and Photon Interactions with Matter

1998, 2008; Bernhard and Close, 2004; Sevilla and Becker, 2004; von Sonntag, 2006; Becker et al.,

2007; Li and Sevilla, 2007; Close, 2008; Kumar and Sevilla, 2008a), and (2) the proton transfer pro-

cesses between the G

•+

:C base pair and the surrounding water (Sharovich et al., 2001; Kobayashi

and

Tagawa, 2003; Kobayashi et al., 2008; Lee et al., 2008).

The

extent of these proton transfer processes depends on the pK

of the ion-radicals involved.

It is also evident from Scheme 19.10 that the intra-base pair proton transfer leads to separation

of charge from spin. Based upon the pK

values of G

•+

in dGuo (ca. 3.9) and C(H

) in 2′-deoxy-

cytidine (ca. 4.5), Steenken had estimated the equilibrium constant for this intra-base pair proton

transfer process, K

, to be ca. 2.5 (Steenken, 1989, 1992, 1997; Adhikary et al., 2009). From this

value of K

, at ambient temperature, both cation radical (G

•+

:C) (30%) and deprotonated neutral

radical (G(-H)

•

:C(+H

)) (70%) forms should exist (Adhikary et al., 2009). This equilibrium constant

suggests that ΔG

= −0.5kcal/mol at 298K (Steenken, 1989, 1992, 1997). For G

•+

:C, theoretical

studies carried out in the gas phase have shown that for the intra-base pair proton transfer along

N1–H bond shown in Scheme 19.10, ΔS (proton transfer) = ca. 0cal/mol/K, and ΔG (proton transfer)=

1.4kcal/mol at 298K (Hütter and Clark, 1996; Bertran et al., 1998; Li et al., 2001). Thus, theory pre-

dicts that G

•+

:C is thermodynamically stable whereas experimental results mentioned above suggest

that

G(-H)

•

:C(+H

) is favored.

Two recent works have provided some additional understanding of the intra-base proton transfer

process (Adhikary et al., 2009; Kumar and Sevilla, 2009a). ESR investigations of C8-deuterated dGuo

(Adhikary et al., 2006c) (see Section 19.5.4) clearly showed that selective deuteration at C-8 on the

guanine moiety in dGuo (G*) resulted in an ESR signal from the guanine cation radical (G*

•+

), which

is easily distinguishable from that of the N1-deprotonated radical, G*(N1–H)

•

(Adhikary et al., 2006c).

Based upon these results, ESR studies employing G* incorporated ssDNA-oligomer TG*T and the

dsDNA-oligomer d[G*CG*CG*CG*C]

have established that in ssDNA, the one-electron oxidized

guanine exists as an equal mixture of G

•+

and G(N1–H)

•

, whereas in dsDNA, only G(N1–H)

•

is found,

or more accurately, G(-H)

•

:C(+H

) as shown in Scheme 19.10 (Adhikary et al., 2009).

We note here that, in ssDNA-oligomer, owing to the lack of base pairing, the formation of

G(N1-H)

•

occurs because of the deprotonation of G

•+

to the solvent; whereas, in the dsDNA-oligomer

d[GCGCGCGC]

, deprotonation takes place from G

•+

to the base paired C by intra-base pair proton

transfer (Adhikary et al., 2009). While the deprotonation in the dsDNA oligomer was complete, for

the ssDNA oligomer it was only 50%. This shows that the base paired cytosine is a better proton

acceptor

than the solvent.

The

second work that aids our understanding of this system involves a theoretical treatment

of the GC cation radical (Kumar and Sevilla, 2009a). As mentioned above, previous theoretical

calculations for the gas phase G

•+

:C pair had predicted an unfavorable intra-base pair proton trans-

fer energy (Hütter and Clark, 1996; Bertran et al., 1998; Li et al., 2001). However, recent theoreti-

cal calculations that included explicit waters of hydration show that, on inclusion of the hydration

shell (ca. 11 waters), the free energy change (ΔG) for intra-base pair proton transfer in the G

•+

pair becomes favorable (ΔG= −0.65kcal/mol) (Kumar and Sevilla, 2009a). Thus both experimental

(Adhikary et al., 2009) and theoretical results (Kumar and Sevilla, 2009a) are in accord and agree

with Steenken (1989) who suggested a favorable ΔG for the intra-base pair proton transfer from

guanine

N1 to cytosine N3 in the G

•+

:C pair.

While it is now clear that the site of interbase proton transfer G

•+

:C is from N1 in guanine, the

site of deprotonation of the DNA cation radical (G

•+

:C) to water is still uncertain. A few recent pulse

radiolysis studies in aqueous solution at ambient temperature (Anderson et al., 2006; Chatgilialoglu

et al., 2006) have proposed that the likely site for deprotonation of the one-electron oxidized gua-

nine in DNA to water is at the exocyclic amine N2 (see Scheme 19.10). DFT calculations (B3LYP/

DZP++) in the gas phase also show that G(N2-H)

•

:C is indeed slightly favored over G(N1-H)

•

by about 1 kcal/mol (Bera and Schaefer, 2005). Thus, the site of deprotonation of one-electron

oxidized guanine in dsDNA to water is likely to be in an equilibrium between N1 and N2 deprotonation,

slightly

favoring N2 (Scheme 19.10) but this needs further conrmation.

PhysicochemicalMechanisms of Radiation-Induced DNA Damage 533

19.5.6 factorS affecting the Sugar radical forMation

froM excitation of cation radicalS

Studies employing DNA- and RNA-nucleosides, nucleotides, and DNA- and RNA-oligomers, as

well as highly polymerized double stranded salmon sperm DNA (see Sections 19.5.3.1 and 19.5.3.2),

have established the following features: (1) the identity of the sugar radical produced via deprot-

onation at specic sites in the sugar moiety and (2) the overall yield of the sugar radical cohort is

critically

inuenced by a number of factors. These are discussed below.

19.5.6.1

site

of p

hosphate

ubstitution

Theoretical calculations (Colson and Sevilla, 1995a,b) predict that phosphate substitution at 3′- or at

5′-site deactivates the formation of a sugar radical at that site by a small increase in the C–H bond

energy. It is evident from Table 19.8 that in dGuo, C5′

•

, C3′

•

, and C1′

•

are produced via photoexcita-

tion of G

•+

; whereas, in 5′-dGMP, preferential formation of C1′

•

occurs along with a small extent

of C3′

•

production. In 3′-dGMP, predominant formation of C5′

•

and observable amount of C1′

•

pro-

duction have been observed. Similarly, in 5′-GMP, primarily C1′

•

formation is observed (Khanduri

etal., 2008). In accordance with theory, both 3′-dAMP and 3′-AMP, show primarily C5′

•

produc-

tion (Adhikary et al., 2006b, 2008b). For 5′-dAMP, both C5′

•

and C3′

•

formation in almost equal

amounts have been observed (Adhikary et al., 2006b). Thus, the theoretical prediction regarding

deactivation of formation of the sugar radical site owing to phosphate substitution at that site seems

to hold for DNA- and RNA-monomers (Adhikary et al., 2005, 2006b, 2008b; Khanduri et al., 2008)

and

for DNA-dinucleoside phosphate TpdG (Adhikary et al., 2006a).

Contrary

to the theoretical predictions (Colson and Sevilla, 1995a,b), signicant C5′

•

forma-

tion has been observed in ssDNA-oligomers of various chain lengths (Adhikary et al., 2007).

Although, in highly polymerized double stranded salmon sperm DNA, only C1′

•

formation has

been found (Adhikary et al., 2005). Moreover, in ssDNA-oligomers, the presence of a 5′-phosphate

in 5′-p-TGGT did not alter the rate and extent of C5′

•

formation (Adhikary et al., 2007). Also, in

the RNA-oligomers, for example, UGGGU, photoexcitation of the guanine cation radical yields

primarily C1′

•

along with an unidentied radical of ca. 28 G doublet (Khanduri et al., 2008).

These ndings clearly suggest the contribution of other factors apart from the site of phosphate

substitution in determining the extent and type of the sugar radicals produced in the cohort as

discussed below.

19.5.6.2 protonation

tate

of o

ne-e

lectron o

xidized

urine

and p

Production of sugar radicals via photoexcitation of one-electron oxidized G in dGuo and in Guo was

found to be pH dependent. It has been observed that both in dGuo (Adhikary et al., 2005) and in

Guo (Khanduri et al., 2008), sugar radical formation occurs via photoexcitation of the cation radical

•+

). However, at pH ≥ 9 where only G(-H)

•

is present, no sugar radical formation occurs. For dAdo

and its derivatives, selective formation of C3′

•

is observed via A(−H)

•

even at pH ca. 12 (Adhikary

al., 2006b).

dsDNA-oligomers containing G, it has been shown that the one-electron oxidized G is the

N1-deprotonated neutral radical, that is, G(-H)

•

(Section 19.5.5) (Adhikary et al., 2009). Thus, no

photoinduced sugar radical formation is expected. Surprisingly, photoexcitation of G(-H)

•

in double

stranded DNA oligomers was indeed found to result in the formation of sugar radicals (Adhikary

et al., 2005). Arguing from the results for dGuo, the one-electron oxidized guanine base should be

protonated for sugar radical formation to take place (Adhikary et al., 2005). It is therefore likely

that reprotonation of the guanine base in the dG(-H)

•

:dC(+H

) in the excited state would precede

the deprotonation from the sugar. In other words, in the excited state, after hole transfer to the

sugar, the equilibrium shown in Scheme 19.10 should rapidly shift to reprotonate guanine, that is, to

produce a ribose cation radical, (dR

+•

)G:dC, thereby allowing deprotonation from the sugar moiety.

Proton transfer in excited states has been extensively studied in aqueous solutions and the rate

534 Charged Particle and Photon Interactions with Matter

of the proton transfer in excited states is often very fast (ca. <ps range) (Agmon, 2005) and thus, the

reprotonation of the guanine base in the dG(-H)

•

:dC(+H

) in the excited state should be rapid (≤10

−12

s).

19.5.6.3 photoexcitation:

ffect

of t

emperature

Table 19.8 clearly demonstrates that the extent of sugar radical production via photoexcitation of the

cation radical in glassy systems increases substantially (from 15%–30% at 77K to ≥80% at 143K)

with temperature. This quantitative increase in the extent of the sugar radical formation has been

found to be a general observation for all the DNA- and RNA-monomers (nucleosides and -tides)

(Adhikary

et al., 2005, 2006b, 2008b; Khanduri et al., 2008).

However,

Table 19.8 shows that, photoexcitation of G

•+

in 5′-dGMP or 5′-GMP samples at 77K

leads to predominant formation of C5′

•

along with an observable amount of C3′

•

and small amounts

of C1′

•

(Adhikary et al., 2005; Khanduri et al., 2008), whereas at 143K, almost exclusively C1′

•

is formed. We note that this type of change in the sugar radical cohort with temperature during

photoexcitation of G

•+

has not been observed for other nucleosides and nucleotides such as dGuo,

3′-dGMP, Guo, dAdo, 3′-dAMP, Ado, and 3′-AMP (Adhikary et al., 2005, 2006b, 2008b; Khanduri

et al., 2008). These results suggest that the molecular relaxation of the excited cation radical at

higher

temperature may change the site of deprotonation in the sugar moiety. This has not yet been

tested

theoretically.

recent report that shows an increase in the rate and extent of intramolecular proton transfer

with decreasing viscosity in protic media provides an explanation for the increasing yield found with

elevated temperatures in glassy systems (Yushchenko et al., 2007). However, this was not found to

be the case for frozen aqueous solutions of dsDNA. As discussed in Section 19.5.3.2, the initial rate

of C1′

•

formation from the photoexcitation of one electron oxidized dsDNA (salmon sperm) has been

found to be independent of temperature in the range 77–180 K (Adhikary et al., 2007). This differ-

ence

is not yet explained but the rigidity of the glass at 77

is a likely factor.

19.5.6.4

wavelength

of p

hotoexcitation

Production of sugar radicals via photoexcitation of one-electron oxidized DNA- and RNA-monomers

(nucleosides and nucleotides) and also in smaller DNA oligomers, for example TGGT, was found

to be relatively independent of wavelength in the range 310–650nm (Adhikary et al., 2005, 2006b,

2008b; Khanduri et al., 2008). However, C1′

•

formation via photoexcitation of one-electron oxi-

dized guanine in dsDNA is wavelength dependent (Adhikary et al., 2005). C1′

•

formation has been

observed in the wavelength range 310–480nm but not for longer wavelengths (Adhikary et al.,

2005). TD-DFT calculations (Adhikary et al., 2005, 2006a; Kumar and Sevilla, 2006), suggest that

this wavelength dependence is likely a result of base-to-base hole transfer during photoexcitation

(see

Figure 19.9).

19.6 ConClusion

As described in this chapter, over the last several years, studies regarding our understanding of the

physicochemical mechanisms of radiation-induced DNA damage have been extended well beyond

the initial ionization event to include the effects of LEE and hole-excited states in the production of

DNA damages including strand breaks. Experimental studies at low and at room temperatures along

with ab initio quantum chemical studies have provided new understandings of these processes. The

site of deprotonation on the sugar moiety in the transient hole-excited states found by experiment

is predicted theoretically to be at those sites with high localization of the hole. Similarly, addition

of a low energy electron to a DNA component resulting in DNA strand breaks is predicted to be

equivalent to the formation of an excited anion radical state, which localizes the electron to a σ*

dissociative state. Excess DNA sugar radicals produced by heavy ions are suggested to be driven

by track-structure processes that produce excitations of ion-radicals. Both electronic and vibrational

PhysicochemicalMechanisms of Radiation-Induced DNA Damage 535

excitations have been suggested to drive ion-radicals to produce sugar radicals and subsequent

strand breaks. Of course, with respect to the in vivo systems (e.g., see Chapter 22), these mechanis-

tic explanations obtained via employing in vitro model systems are tentative and will need further

studies

to ascertain the validity and the extent of their application.

aCknowledgments

The authors thank the National Cancer Institute of the National Institutes of Health (Grant

RO1CA45424)

for support and Dr. Anil Kumar for his help in preparing this manuscript.

reFerenCes

Adhikary, A., Malkhasian, A. Y. S., Collins, S., Koppen, J., Becker, D., and Sevilla, M. D. 2005. UVA-visible

photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures. Nucleic

Acids Res.

33: 5553–5564.

Adhikary,

A., Kumar, A., and Sevilla, M. D. 2006a. Photo-induced hole transfer from base to sugar in DNA:

Relationship

to primary radiation damage. Radiat. Res. 165: 479–484.

Adhikary,

A., Becker, D., Collins, S., Koppen, J., and Sevilla, M. D. 2006b. C5′- and C3′-sugar radicals pro-

duced via photo-excitation of one-electron oxidized adenine in 2′-deoxyadenosine and its derivatives.

Nucleic Acids Res.

34: 1501–1511.

Adhikary,

A., Kumar, A., Becker, D., and Sevilla, M. D. 2006c. The guanine cation radical: Investigation of

deprotonation

states by ESR and DFT. J. Phys. Chem. B 110: 24171–24180.

Adhikary,

A., Collins, S., Khanduri, D., and Sevilla, M. D. 2007. Sugar radicals formed by photo-excitation of

guanine

cation radical in oligonucleotides. J. Phys. Chem. B 111: 7415–7421.

Adhikary,

A.,

Kumar,

A.,

Khanduri, D., and Sevilla, M. D. 2008a.

The

effect of base stacking on the acid-base

properties of the adenine cation radical [A

•+

] in solution: ESR and DFT studies. J. Am. Chem. Soc. 130:

10282–10292.

Adhikary, A., Khanduri, D., Kumar, A., and Sevilla, M. D. 2008b. Photo-excitation of adenine cation radical

•+

] in the near UV-vis region produces sugar radicals in adenosine and in its nucleotides. J. Phys. Chem.

112: 15844–15855.

Adhikary,

A., Khanduri, D., and Sevilla, M. D. 2009. Direct observation of the hole protonation state and hole

localization

site in DNA-oligomers. J. Am. Chem. Soc. 131: 8614–8619.

Agmon, N. 2005. Elementary steps in excited-state proton transfer. J. Phys. Chem. A 109: 13–35.

Anderson,

R. F., Shinde, S. S., and Maroz, A. 2006. Cytosine-gated hole creation and transfer in DNA in aque-

ous

solution. J. Am. Chem. Soc. 128: 15966–15967.

Arkin,

M. R., Stemp, E. D. A., Pulver, S. C., and Barton, J. K. 1997. Long-range oxidation of guanine by

Ru(III)

in duplex DNA. Chem. Biol. 4: 389–400.

Augustyn,

K. E., Genereux, J. C., and Barton, J. K. 2007. Distance-independent DNA charge transport across

adenine tract. Angew. Chem. Int. Ed. 46: 5731–5733.

Bald,

I., Kopyra, J., and Illenberger, E. 2006. Selective excision of C5 from D-ribose in the gas phase by low-

energy electrons (0–1 eV): Implications for the mechanism of DNA damage. Angew. Chem. Int. Ed. 45:

4851–4855.

Bald, I., Dabkowska, I., and Illenberger, E. 2008. Probing biomolecules by laser-induced acoustic desorp-

tion: Electrons at near zero electron volts trigger sugar-phosphate cleavage. Angew. Chem. Int. Ed. 47:

8518–8520.

Becker, D. and Sevilla, M. D. 1993. The chemical consequences of radiation-damage to DNA. Adv. Radiat.

Biol.

17: 121–180.

Becker,

D. and Sevilla, M. D. 1998. Radiation damage to DNA and related biomolecules. In Royal Society

of Chemistry Specialist Periodical Report: Electron Spin Resonance, B. C. Gilbert, M. J. Davies, and

D.M.Murphy

(eds.),

Vol.

16, pp. 79–115. Cambridge, U.K.:

The

Royal Society of Chemistry.

Becker,

D. and Sevilla, M. D. 2008. EPR studies of radiation damage to DNA and related molecules. In Royal

Society of Chemistry Specialist Periodical Report: Electron Spin Resonance, B. C. Gilbert, M. J. Davies,

and

D. M. Murphy (eds.),

Vol.

21, pp. 33–58. Cambridge, U.K.:

The

Royal Society of Chemistry.

Becker,

D., Razskazovskii, Y., Callaghan, M. U., and Sevilla, M. D. 1996. Electron spin resonance of DNA

irradiated with a heavy-ion beam (

): Evidence for damage to the deoxyribose phosphate backbone.

Radiat. Res.

146: 361–368.

536 Charged Particle and Photon Interactions with Matter

Becker, D., Bryant-Friedrich, A., Trzasko, C., and Sevilla, M. D. 2003. Electron spin resonance study of DNA

irradiated with an argon-ion beam: Evidence for formation of sugar phosphate backbone radicals. Radiat.

Res.

160: 174–185.

Becker,

D., Adhikary, A., and Sevilla, M. D. 2007. The role of charge and spin migration in DNA radiation

damage. In Charge Migration in DNA Physics, Chemistry and Biology Perspectives, T. Chakraborty

(ed.),

p. 139. Berlin/Heidelberg, Germany: Springer-Verlag.

Becker,

D., Adhikary, A., and Sevilla, M. D. 2010. Mechanism of radiation induced DNA damage: Direct

effects. In Recent Trends in Radiation Chemistry, B. S. M. Rao and J. Wishart (eds.), pp. 509–542.

Singapore/New

Jersey/London, U.K.:

World

Scientic Publishing Co.

Bera,

P. P. and Schaefer III, H. F. 2005. (G-H)

•

-C and G-(C-H)

•

radicals derived from the guanine-cytosine base

pair

cause DNA subunit lesions. Proc. Natl. Acad. Sci. USA 102: 6698–6703.

Bernhard,

W. A.

1981. Solid-state radiation of DNA:

The

bases. Adv. Radiat. Biol. 9: 199–280.

Bernhard,

W. A. and Close, D. M. 2004. DNA damage dictates the biological consequences of ionizing

irradiation: The chemical pathways. In Charged Particle and Photon Interactions with Matter. Chemical,

Physicochemical and Biological Consequences with Applications, A. Mozumdar and Y. Hatano (eds.),

pp.

431–470. New

York/Basel,

Switzerland: Marcel Dekker, Inc.

Bertran,

J., Oliva, A., Rodriguez-Santiego, L., and Sodupe, M. 1998. Single versus double proton-transfer reac-

tions

Watson-Crick

base pair radical cations.

theoretical study. J. Am. Chem. Soc. 120: 8159–8167.

Boudaïffa,

B., Cloutier, P., Hunting, D., Huels, M. A., and Sanche, L. 2000. Resonant formation of DNA strand

breaks

by low-energy (3–20

eV)

electrons. Science 287: 1658–1660.

Bowman,

M. K., Becker, D., Sevilla, M. D., and Zimbrick, J. D. 2005. Track structure in DNA irradiated with

heavy

ions. Radiat. Res. 163: 447–454.

Burrow,

P. D., Gallup, G. A., Scheer, A. M., Deni, S., Ptasinska, S., Mark, T., and Scheier, P. 2006. Vibrational

Feshbach

resonances in uracil and thymine. J. Chem. Phys. 124,124310.

Burrow,

P. D., Gallup, G. A., and Modelli, A. 2008. Are there pi* shape resonances in electron scattering from

phosphate

groups? J. Phys. Chem. A 112: 4106–4113.

Cadet,

J., Bourdat, A.-G., D’Ham, C., Duarte, V., Gasparutto, D., Romieu, A., and Ravanat, J.-L. 2000.

Oxidative base damage to DNA: Specicity of base excision repair enzymes. Mutat. Res. 462: 121–128.

Cai, Z. and Sevilla, M. D. 2000. Electron spin resonance study of electron transfer in DNA: Inter-double-strand

tunneling

processes. J. Phys. Chem. B 104: 6942–6949.

Cai,

Z. and Sevilla, M. D. 2004. Studies of excess electron and hole transfer in DNA at low temperature. In

Long Range Transfer in DNA II: Topics in Current Chemistry, G. B. Shuster (ed.), Vol. 237, pp. 103–127.

Berlin/Heidelberg,

Germany/New

York:

Springer-Verlag.

Cai,

Z., Gu, Z., and Sevilla, M. D. 2001. Electron spin resonance study of electron and hole transfer in

DNA: Effects of hydration, aliphatic amine cations, and histone proteins. J. Phys. Chem. B 105:

6031–6041.

Chatgilialoglu, C., Caminal, C., Guerra, M., and Mulazzani, Q. G. 2005. Tautomers of one-electron-oxidized

guanosine.

Angew. Chem. Int. Ed. 44: 6030–6032.

Chatgilialoglu,

C., Caminal, C., Altieri, A., Vougioukalakis, G. C., Mulazzani, Q. G., Gimisis, T., and Guerra, M.

2006. Tautomerism

in the guanyl radical. J. Am. Chem. Soc. 128: 13796–13805.

Chatterjee,

A. 2006. Importance of collaborative research between theoretical modelers and experimentalists,

Abstracts, Fifty-Third Annual Meeting of the Radiation Research Society, Philadelphia, PA, p. 3.

Chatterjee,

A. and Holley, W. R. 1993. Computer-simulation of initial events in the biochemical-mechanisms

DNA-damage. Adv. Radiat. Biol. 17: 181–226.

Close,

D. M. 2008. From the primary radiation induced radicals in DNA constituents to strand breaks: Low

temperature EPR/ENDOR studies. In Radiation Induced Molecular Phenomena in Nucleic Acid:

A Comprehensive Theoretical and Experimental Analysis, M. K. Shukla and J. Leszczynski (eds.),

pp.493–529.

Berlin/Heidelberg, Germany/New

York:

Springer-Verlag.

Colson,

A.-O. and Sevilla, M. D. 1995a. Elucidation of primary radiation damage in DNA through application

ab initio molecular orbital theory. Int. J. Radiat. Biol., 67: 627–645.

Colson,

A.-O. and Sevilla, M. D. 1995b. Structure and relative stability of deoxyribose radicals in a model DNA

backbone:

ab initio molecular orbital calculations. J. Phys. Chem. 99: 3867–3874.

Conwell,

E. M. 2005. Charge transport in DNA in solution: The role of polarons. Proc. Natl. Acad. Sci. USA

102:

8795–8799.

Conwell, E. M. and Rakhmanova, S.

2000. Polarons in DNA. Proc. Natl. Acad. Sci. USA 97: 4556–4560.

Cullis,

P. M., Malone, M. E., and Merson-Davies, L. A. 1996. Guanine radical cations are precursor of

7,8-dihydro-8-oxo-2′-deoxyguanosine but are not precursor of immediate strand breaks in DNA. J. Am.

Chem. Soc.

118: 2775–2781.

PhysicochemicalMechanisms of Radiation-Induced DNA Damage 537

Dawidzik, J. B., Budzunzki, E. E., Patrzyc, H. B., Cheng, H.-C., Iijima, H., Alderfer, J. L., Tabaczynski, W. A.,

Wallace, J. C., and Box, H. C. 2004. Dihydrothymine lesion in x-irradiated DNA: Characterization at the

molecular

level and detection in cells. Int. J. Radiat. Biol. 80: 355–361.

Lara, C. M., Jenner, T. J., Townsend, K. M., Marsden, S. J., and O’Neill, P. 1995. The effect of dimethyl

sulfoxide on the induction of DNA double-strand breaks in V79-4 mammalian cells by alpha particles.

Radiat. Res.

144: 43–49.

Debije,

M. G. and Bernhard, W. A. 2000. Electron and hole transfer induced by thermal annealing of crystalline

DNA

x-irradiated at 4

J. Phys. Chem. B 104: 7845–7851.

Drummond,

T. G., Hill, M. G., and Barton, J. K. 2003. Electrochemical DNA sensors. Nat. Biotechnol. 21:

1192–1199.

Fink, H.-W. and Schönenberger, C. 1999. Electrical conduction through DNA molecules. Nature 398: 407–410.

Friedland, W., Jacob, P., Bernhardt, P., Paretzke, H. G., and Dingfelder, M. 2003. Simulation of DNA damage

after

proton irradiation. Radiat. Res. 159: 401–410.

Gasper,

S. M. and Schuster, G. B. 1997. Intramolecular photoinduced electron transfer to anthroquinones

linked to duplex DNA: Effect of gaps and traps on long range of radical cation migration. J. Am. Chem.

Soc.

119: 12762–12771.

Giese,

B. 2000. Long distance charge transport in DNA: The hopping mechanism. Acc. Chem. Res. 33:

631–636.

Giese,

B. 2002. Long-distance electron transfer through DNA. Annu. Rev. Biochem. 71: 51–70.

Giese,

B., Amaudrut, J., Köhler, A.-K., Spormann, M., and Wessely, S. 2001. Direct observation of the hole

transfer

through DNA by hopping between adenine bases and by tunneling. Nature 412: 318–320.

Goodhead,

D. T., Leenhouts, H. P., Paretzke, H. G., Terrisol, M., Nikjoo, H., and Blaauboer, R. 1994. Track

structure approaches to the interpretation of radiation effects on DNA. Radiat. Prot. Dosimetry 52:

217–223.

Grozema, F. C. and Siebbeles, L. D. 2007. Mechanism and absolute rates of charge transfer through DNA. In

Charge Migration in DNA Physics, Chemistry and Biology Perspectives, T. Chakraborty (ed.), pp. 21–43.

Berlin/Heidelberg,

Germany: Springer-Verlag.

Hada,

M. and Georgakilas, A. G. 2008. Formation of clustered DNA damage after high-LET irradiation: A

review.

J. Radiat. Res. 49: 203–210.

Henderson,

P. T., Jones, D., Hampikian, G., Kan, Y. Z., and Schuster, G. B. 1999. Long-distance charge trans-

port in duplex DNA: The phonon-assisted polaron-like hopping mechanism. Proc. Natl. Acad. Sci. USA

96:

8353–8358.

Hill,

1999. Radiation damage to DNA:

The

importance of track structure. Radiat. Meas. 31: 15–23.

Hütter,

M. and Clark, T. 1996. On the enhanced stability of the guanine-cytosine base-pair radical cation. J. Am.

Chem. Soc.

118: 7574–7577.

Jakob,

B., Scholz, M., and Taucher-Scholz, G. 2003. Biological imaging of heavy charged-particle tracks.

Radiat. Res.

159: 676–684.

Jones,

G. D., Milligan, J. R., Ward, J. F., Calabro-Jones, P. M., and Aguilera, J. A. 1993. Yield of strand breaks

as a function of scavenger concentration and LET for SV40 irradiated with

He ions. Radiat. Res. 136:

190–196.

Jortner, J., Bixon, M., Langenbacher, T., and Michel-Beyerle, M. E. 1998. Charge transfer and transport in

DNA.

Proc. Natl. Acad. Sci. USA 95: 12759–12765.

Joy,

A., Ghosh, A. K., and Schuster, G. B. 2006. One-electron oxidation of DNA oligomers that lack guanine:

Reaction and strand cleavage at remote thymines by long-distance radical cation hopping. J. Am. Chem.

Soc.

128: 5346–5347.

Kawai,

K. and Majima, T. 2005. Spectroscopic investigation of oxidative hole transfer via adenine hopping in

DNA. In Charge Transfer in DNA: From Mechanism to Application, H.-A. Wagenknecht (ed.), p. 117.

Weinheim,

Germany:

Wiley-VCH Verlag

GmbH & Co. KGaA.

Khanduri,

D., Collins, S., Kumar, A., Adhikary, A., and Sevilla, M. D. 2008. Formation of sugar radicals in

RNA model systems and oligomers via excitation of guanine cation radical. J. Phys. Chem. B 112:

2168–2178.

Kobayashi, K. and Tagawa, S. 2003. Direct observation of guanine radical cation deprotonation in duplex DNA

using

pulse radiolysis. J. Am. Chem. Soc. 125: 10213–10218.

Kobayashi,

K., Yamagami, R., and Tagawa, S. 2008. Effect of base sequence and deprotonation of guanine

cation

radical in DNA. J. Phys. Chem. B 112: 10752–10757.

Kraft, G. and Kramer, M. 1993. Linear-energy-transfer and track structure. Adv. Radiat. Biol. 17: 1–52.

Kumar,

A. and Sevilla, M. D. 2006. Photoexcitation of dinucleoside radical cations: A time-dependent density

functional

study. J. Phys. Chem. B 110: 24181–24188.

538 Charged Particle and Photon Interactions with Matter

Kumar, A. and Sevilla, M. D. 2007. Low-energy electron attachment to 5″-thymidine monophosphate: Modeling

single

strand breaks through dissociative electron attachment. J. Phys. Chem. B 111: 5464–5474.

Kumar,

A. and Sevilla, M. D. 2008a. Radiation effects on DNA: Theoretical investigations of electron, hole

and excitation pathways to DNA damage. In Radiation Induced Molecular Phenomena in Nucleic Acid:

A Comprehensive Theoretical and Experimental Analysis, M. K. Shukla and J. Leszczynski (eds.),

pp.577–617.

Berlin/Heidelberg, Germany/New

York:

Springer-Verlag.

Kumar,

A. and Sevilla, M. D. 2008b. The role of pi sigma* excited states in electron-induced DNA strand break

formation: A

time-dependent density functional theory study. J. Am. Chem. Soc. 130: 2130–2131.

Kumar,

A. and Sevilla, M. D. 2009a. Inuence of hydration on proton transfer in the guanine-cytosine radical

cation (G(

•+

)-C) base pair: A density functional theory study. J. Phys. Chem. B 113(33): 11359–11361.

Article ASAP

DOI: 10.1021/jp903403d, Publication Date (Web): June 1, 2009.

Kumar,

A. and Sevilla, M. D. 2009b. Role of excited states in low-energy electron (LEE) induced strand breaks

DNA model systems: Inuence of aqueous environment. ChemPhysChem. 10: 1426–1430.

Vere, T., Becker, D., and Sevilla, M. D. 1996.Yields of

•

OH in gamma-irradiated DNA as a function of DNA

hydration:

Hole transfer in competition with

•

OH formation. Radiat. Res. 145: 673–680.

Lee, Y. A., Durandin, A., Dedon, P. C., Geacintov, N. E., and Sharovich, V. 2008. Oxidation of guanine in

G, GG, and GGG sequence contexts by aromatic pyrenyl radical cations and carbonate radical anions:

Relationship between kinetics and distribution of alkali-labile lesions. J. Phys. Chem. B 112: 1834–1844.

Lewis,

F. D. 2005. DNA molecular photonics. Photochem. Photobiol. 81: 65–72.

Lewis,

F. D., Llu, X., Llu, J., Miller, S. E., Hayes, R. T., and Wasielewski, M. R. 2000. Direct measurement of

hole

transport dynamics in DNA. Nature 406: 51–53.

Lewis,

F. D., Letsinger, R. L., and Wasielewski, M. R. 2001. Dynamics of photoinduced charge transfer and

hole

transport in synthetic DNA hairpins. Acc. Chem. Res. 34: 159–170.

Lewis,

F. D., Daublain, P., Zhang, L., Cohen, B., Vura-Weis, J., Wasielewski, M. R., Sharovich, V., Wang, Q.,

Raytchev, M., and Fiebig, T. 2008. Reversible bridge-mediated excited-state symmetry breaking in

stilbene-linked

DNA dumbbells. J. Phys. Chem. B 112: 3838–3843.

Li,

X. F. and Sevilla, M. D. 2007. DFT treatment of radiation produced radicals in DNA model systems. Adv.

Quantum Chem.

2007, 52: 59–87.

Li,

X., Cai, Z., and Sevilla, M. D. 2001. Investigation of proton transfer within DNA base pair anion and cation

radicals

by density functional theory (DFT). J. Phys. Chem. B 105: 10115–10123.

Li,

M.-J., Liu, L., Fu,Y., and Guo, Q.-X. 2005. Development of an ONIOM-G3B3 method to accurately predict

C-H and N-H bond dissociation enthalpies of ribonucleosides and deoxyribonucleosides. J. Phys. Chem.

109: 13818–13826.

Li,

M.-J., Liu, L., Fu, Y., and Guo, Q.-X. 2006. Signicant effects of phosphorylation on relative stabilities

of DNA and RNA sugar radicals: Remarkably high susceptibility of H-2″ abstraction in RNA. J. Phys.

Chem. B

110: 13582–13589.

Liu,

T. and Barton, J. K. 2005. DNA electrochemistry through the base pairs not the sugar-phosphate backbone.

J. Am. Chem. Soc.

127: 10160–10601.

Luo,

Q., Li, Q. S., Xie,Y., and Schaefer III, H. F. 2005. Radicals derived from guanine: Structures and energet-

ics.

Collect. Czech. Chem. Commun. 70: 826–836.

Ly,

D., Sanii, L., and Schuster, G. B. 1999. Mechanism of charge transport in DNA: Internally-linked anthra-

quinone

conjugates support phonon-assisted polaron hopping. J. Am. Chem. Soc. 121: 9400–9410.

Magee,

J. L. and Chatterjee, A. 1987. Track reactions of radiation chemistry. In Kinetics of Nonhomogenous

Processes,

G. R. Freeman (ed.), pp. 171–214. New

York: Wiley.

Mundy, C. J., Colvin, M. E., and Quong, A. A. 2002. Irradiated guanine: A Car-Parrinello molecular dynamics

study

of dehydrogenation in the presence of an OH radical. J. Phys. Chem. A 106: 10063–10071.

Naumov,

S. and von Sonntag, C. 2008. Guanine-derived radicals: Dielectric constant-dependent stability and

UV/Vis

spectral properties:

DFT study. Radiat. Res. 169: 364–372.

Nelson,

D. and Symons, M. C. R. 1977. Unstable intermediates. Part 169. Electron capture processes in organic

phosphates: An

electron spin resonance study. J. Chem. Soc. Perkin II 286–293.

Nelson,

D. J., Symons, M. C. R., and Wyatt, J. L. 1993. Electron-paramagnetic-resonance studies of irradiated

D-glucose-6-phosphate

ions: Relevance to DNA. J. Chem. Soc. Faraday Trans. 89: 1955–1958.

Nikjoo,

H. and Uehara, S. 2004. Track structure studies of biological systems. In Charged Particle and Photon

Interactions with Matter. Chemical, Physicochemical and Biological Consequences with Applications,

Mozumdar and

Hatano (eds.), pp. 491–531. New

York/Basel,

Switzerland: Marcel Dekker, Inc.

Nocek,

J. M., Zhou, J. S., de Forest, S., Priyadarshy, S., Beratan, D. N., Onuchic, J. N., and Hoffman, B.M.

1996. Theory and practice of electron transfer within protein-protein complexes: Application to the

multi-domain

binding of cytochrome c by cytochrome c peroxidase. Chem. Rev. 96: 2459–2489.

PhysicochemicalMechanisms of Radiation-Induced DNA Damage 539

Núñez, M. E., Hall, D. B., and Barton, J. K. 1999. Long-range oxidative damage to DNA: Effects of distance

and

sequence. Chem. Biol. 6: 85–97.

Núñez,

M. E., Holmquist, G. P., and Barton, J. K. 2001. Evidence for DNA charge transport in the nucleus.

Biochemistry

40: 12465–12471.

Núñez,

M. E., Noyes, K. T., and Barton, J. K. 2002. Oxidative charge transport through DNA in nucleosome

core

particles. Chem. Biol. 9: 403–415.

O’Neill,

P. 2001. Radiation-induced damage in DNA. In Radiation Chemistry: Present Status and Future

Trends,

C. D. Jonah and B. S. M. Rao (eds.), pp. 585–622.

Amsterdam,

the Netherlands: Elsevier.

Osakada,

Y., Kawai, K., Fujitsuka, M., and Majima, T. 2008. Charge transfer in DNA assemblies: Effects of

sticky

ends. Chem. Commun. 23: 2656–2658.

Pan,

X. and Sanche, L. 2006. Dissociative electron attachment to DNA basic constituents: The phosphate

group.

Chem. Phys. Lett. 421: 404–408.

Panajotovic,

R., Martin, F., Cloutier, P. C., Hunting, D., and Sanche, L. 2006. Effective cross sections for pro-

duction

of single-strand breaks in plasmid DNA by 0.1 to 4.7

electrons. Radiat. Res. 165: 452–459.

Pezeshk,

A., Symons, M. C. R., and McClymont, J. D. 1996. Electron movement along DNA strands: Use of

intercalators

and electron paramagnetic resonance spectroscopy. J. Phys. Chem. 100: 18562–18566.

Porath,

D., Bezryadin, A., de Vries, S., and Dekker, C. 2001. Direct measurements of electrical transport

through

DNA molecules. Nature 403: 635–637.

Purkayastha,

S., Milligan, J. R., and Bernhard, W. A. 2005. Correlation of free radical yields with strand

break yields produced in plasmid DNA by the direct effect of ionizing radiation. J. Phys. Chem. B 109:

16967–16973.

Purkayastha, S., Milligan, J. R., and Bernhard, W. A. 2006a. The role of hydration in the distribution of free

radical

trapping in directly ionized DNA. Radiat. Res. 166: 1–8.

Purkayastha,

S., Milligan, J. R., and Bernhard, W. A. 2006b. An investigation into the mechanisms of

DNA strand breakage by direct ionization of variably hydrated plasmid DNA. J. Phys. Chem. B 110:

26286–26291.

Purkayastha, S., Milligan, J. R., and Bernhard, W. A. 2007. On the chemical yield of base lesions, strand breaks,

and clustered damage generated in plasmid DNA by the direct effect of x rays. Radiat. Res. 168: 357–366.

Ravanat, J.-L., Saint-Pierre, C., and Cadet, J. 2003. One electron oxidation of the guanine moiety of 2′-deoxy-

guanosine:

Inuence of 8-oxo-7,8-dihydro-2′-deoxyguanosine. J. Am. Chem. Soc. 125: 2030–2031.

Razskazovskiy,

Y., Debije, M. G., and Bernhard, W. A. 2003a. Strand breaks produced in X-írradiated crystal-

line

DNA: Inuence of base sequence. Radiat. Res. 159: 663–669.

Razskazovskiy,

Y., Debije, M. G., Howerton, S. B., Williams, L. D., and Bernhard, W. A. 2003b. Strand breaks

x-irradiated crystalline DNA:

Alternating

CG oligomers. Radiat. Res. 160: 334–339.

Saito,

I., Nakamura, T., Nakatani, K.,Yoshioka, Y., Yamaguchi, K., and Sugiyama, H. 1998. Mapping of the hot

spots for DNA damage by one-electron oxidation: Efcacy of GG doublets and GGG triplets as a trap in

long-range

hole migration. J. Am. Chem. Soc. 120: 12686–12687.

Sanche,

L. 2008. Low energy electron damage to DNA. In Radiation Induced Molecular Phenomena in Nucleic

Acid: A Comprehensive Theoretical and Experimental Analysis, M. K. Shukla and J. Leszczynski (eds.),

pp.

531–575. Berlin/Heidelberg, Germany/New

York:

Springer-Verlag.

Sanderud,

A. and Sagstuen, E. 1996. EPR study of X-irradiated hydroxyalkyl phosphate esters: Phosphate radi-

cal formation in polycrystalline glucose phosphate, ribose phosphate and glycerol phosphate salts at 77

and

295

J. Chem. Soc. Faraday Trans. 92: 995–999.

Schuhmacher,

H. and Dangendorf, V. 2002. Experimental tools for track structure investigations: New

approaches

for dosimetry and microdosimetry. Radiat. Prot. Dosimetry. 2002, 99: 317–323.

Schuster,

G. B. 2000. Long-range charge transfer in DNA: Transient structural distortions control the distance

dependence.

Acc. Chem. Res. 33: 253–260.

Schuster,

G. B. (ed.) 2004. Long Range Charge Transfer in DNA. I and II, Topics in Current Chemistry. Berlin/

Heidelberg,

Germany: Springer-Verlag.

Sevilla,

M. D. and Becker, D. 2004. ESR studies of radiation damage to DNA and related biomolecules. In Royal

Society of Chemistry Specialist Periodical Report: Electron Spin Resonance, B. C. Gilbert, M. J. Davies,

and D. M. Murphy (eds.), Vol. 19, pp. 243–278. Cambridge, U.K.: The Royal Society of Chemistry.

Sharovich, V., Dourandin, A., and Geacintov, N. E. 2001. Proton-coupled electron-transfer reactions at a dis-

tance

in DNA duplexes: Kinetic deuterium isotope effect. J. Phys. Chem. B 105: 8431–8435.

Shao,

F., O’Neill, M. A., and Barton, J. K. 2004. Long-range oxidative damage to cytosines in duplex DNA.

Proc. Natl. Acad. Sci. USA

101: 17914–17919.

Sharma,

K. K., Purakayastha, S., and Bernhard, W.A. 2007. Unaltered free base release from d(CGCGCG)

pro-

duced by the direct effect of ionizing radiation at 4K and room temperature. Radiat. Res. 167: 501–507.