Dynamic Behavior of Secondary Electrons in Liquid Water at the

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Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism Takeshi Kai, Akinari Yokoya, Masatoshi Ukai, Kentaro Fujii, and Ritsuko Watanabe J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.6b05929 • Publication Date (Web): 03 Oct 2016 Downloaded from http://pubs.acs.org on October 3, 2016

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The Journal of Physical Chemistry

Dynamic Behavior of Secondary Electrons in Liquid Water at the Earliest Stage upon Irradiation: Implications for DNA Damage Localization Mechanism Takeshi Kai*1, Akinari Yokoya2, Masatoshi Ukai3, Kentaro Fujii2, and Ritsuko Watanabe2 1

Nuclear Science and Engineering Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai, Naka, Ibaraki 319-1195, Japan 2

Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological

Science and Technology, 2-4 Shirakatashirane, Tokai, Naka, Ibaraki 319-1195, Japan 3 Department of Applied Physics, Tokyo University of Agriculture and Technology, Koganei-shi, Tokyo 184-8588, Japan

AUTHOR INFORMATION Corresponding author * Phone No.: +81-29-282-5583 Fax No.: +81-29-282-6768 E-mail address: [email protected]

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ACS Paragon Plus Environment


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ABSTRACT: To clarify the formation of radiation damage in DNA, the dynamic behavior of low-energy secondary electrons produced by ionizing radiation in water was studied by using a dynamic Monte Carlo code that considers the Coulombic force between electrons and their parent cations. The calculated time evolution of the mean energy, total track length, and mean traveling distance of the electrons indicated that the prehydration of the electrons occurs competitively with thermalization on a timescale of hundreds of femtoseconds. The decelerating electrons are gradually attracted to their parent cations by Coulombic force within hundreds of femtoseconds, and finally about 12.6% electrons are distributed within 2 nm of the cations. The collision fraction for ionization and electronic excitation within 1 nm of the cation was estimated to be about 40%. If these electrons are decelerated in a living cell, they may cause highly localized lesions around a cation in a DNA molecule through additional dissociative electron transfer (DET) as well as ionization and electronic excitation (EXC), possibly resulting in cell death or mutation.

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Introduction When primary ionizing radiation, such as high-energy X-rays, γ-rays, or charged particles, traverses a living cell, it produces numerous single spurs consisting of secondary products including free radicals and low-energy secondary electrons. The primary ionizing radiation and the secondary products interact with genomic DNA in the cell to produce DNA damage, such as strand breaks, oxidative (or reductive) nucleobase lesions, or apurinic/apyrimidinic (AP) sites. Some damage may cause harmful biological effects, such as cell death or mutation, particularly when the lesions are spatially localized within one or two helical turns (3.4 nm per helical turn) of the DNA molecule, which is known as a clustered DNA damage site1,2. Various factors dictate the damage distribution. The actions of diffusible free radicals, such as OH radicals produced by water radiolysis, have been studied by using both experimental and computer modeling approaches3,4 in terms of damage induction. These radicals randomly react with DNA after diffusion in a medium over picosecond to nanosecond time scales, and this is known as the indirect effect of radiation. The energy deposited in DNA by primary radiation and secondary electrons produced by ionization also react with DNA, known as the direct effect of radiation5. Over the last few decades, primary electron transport in the high-energy region above 1 keV has been thoroughly investigated by a number of simulations with conventional track structure code (see review by Nikjoo et al.6). However, the role in DNA damage induction of low-energy electrons below several hundred electronvolts is still far from being understood because of the experimental difficulties in 3



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using low-energy electrons, particularly below 100 eV, as they have a limited penetration depth in most materials. Recent advances in experimental techniques have made it possible to inject low-energy electrons into samples under high vacuum. This has revealed that DNA strand breaks can be induced via dissociative electron attachment (DEA)7. Although it is widely recognized that, in addition to ionization or electronic excitation from electron impact, DEA contributes to DNA damage induction, the spatial distribution of the strand breaks in relation to the induction of clustered DNA damage sites has not been clarified. Furthermore, using a photolysis technique, it was revealed that prehydrated electrons (e−pre) also induce various types of DNA damage through dissociative electron transfer (DET) in unit molecules of DNA, nucleotides, or nucleobases8. The efficiency of reductive DNA damage induction through DET is nearly double that of oxidative damage by OH radical action9. The contributions of both DEA and DET to clustered DNA damage induction should be considered in theoretical studies to determine the relevance of the damage distribution in DNA molecules. To specify the role of low-energy electrons in localized damage in a DNA molecule, we investigated the successive deceleration of secondary electrons in water. A dynamic Monte Carlo code for simulating the electron trajectories in water was developed. The code used cross sections of the rotation excitation of the gas phase of water to include the Coulombic field of the parent cation produced in water by high-energy electron impact10. We calculated the cross sections for the liquid phase11, which had not been experimentally or theoretically obtained. The rotation cross sections 4


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were unexpectedly three orders of magnitude smaller than those of the gas phase. Thus, we updated our code by using the cross sections for the liquid phase to calculate thermalization lengths of the low-energy electrons in liquid water in the energy region from 0.1 eV to 100 keV. In the energy region of 1 eV or less, we suggested that prehydration of the epithermal electrons might competitively occur with thermalization, and we determined the degree of lesion clustering in the DNA molecule12. In this study, we investigate the dynamic behavior of the secondary electrons further, considering the temporal evolution of the Coulombic field among parent cations and electrons. The trajectory of the electrons is strongly affected by the Coulombic field of the cation to form a single spur with the parent cation. The temporal evolution of electron deceleration has been clarified on a femtosecond timescale. This is a crucial aspect of the earliest stage of water radiolysis for estimating the clustering degree of DNA lesions because the distribution of the decelerated electrons may be similar to that of the prehydrated electrons, which can induce DNA damage through DET. The localization of DNA lesions and the proposed scenario of clustered DNA damage involved in DET in a single spur are discussed.

Simulation methods Our code comprises the simulation of electron dynamics with a Newtonian equation and the calculation of collisions between electrons and liquid water with a Monte Carlo method10–12. Few 5



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ionization or excitation cross sections of DNA in liquid water for low-energy electron impact have been reported. However, ionization cross sections of DNA molecules in the gas phase for electron impact have been reported by Bernhardt and Paretzke13, indicating that the cross section for the DNA is comparable to, or at most 1.4 times greater than, that for liquid water. Thus, we assumed that using the cross sections for liquid water instead of those of DNA would not matter for simulating the spatial distribution of radiation damage of DNA in liquid water. The cross sections used in this study have already been presented in our previous papers11,12. The specific heat capacity for vibration and rotation was assumed to be determined by the number of microscopic states based on normalization with the number of atoms (as for Debye's specific heat formula). Thus, the heat capacity could be scaled by atomic density. DNA molecules were assumed not to evaporate. Based on these assumptions, we calculated the electron deceleration in water, instead of in DNA, to simulate the spatial distribution of DNA lesions. We assumed that the cross sections of a DNA molecule could be replaced with that of liquid water. In terms of atomic species, this corresponds to approximating carbon, nitrogen and phosphorus atoms with oxygen atoms. Although these atoms are several angstroms in size, the size of the Coulombic fields of the carbon, nitrogen, and phosphorus ions are similar to that of the oxygen ion in spatial nanoscale because the size depends approximately on the ionic charge. Our method for simulating the electron trajectory is as follows. We assumed that the electrons and the parent cations are finite-sized particles with radius a and charge e to avoid divergence near the center of the 6


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Coulombic potential. The potentials, Φ(r), at the inner and outer regions of the particles are described by e

(r ≥ a ),

4πεr

Φ(r ) =

1

4πε ∫

∞

−∞

e dr ' = ' r−r

(1)

(

e 3a 2 − r 2 8πεa 3

)

(r < a ),

where e is the elementary charge, ε is the dielectric constant of water, and r (= |r|) is the distance from the center of the charged particle. We assumed that radius a of a charged particle was 1.5 Å10. We solved a Newtonian equation by considering the Coulombic field of the electrons or parent cation

m

d v l = ∑ Flj , dt j ≠l (2)

d xl = vl , dt

where

Flj = ±

e2 rlj 4πεrlj3

(r

≥a,

Flj = ±

e2 rlj 4πεa 3

(r

10 nm

Total

8.6%

4.0%

42.2%

45.2%

100%

(fate of the

(recombination

(DET through

(DET or eaq through

(DET or eaq through

electron)

with the parent

prehydration)

prehydration)

prehydration)

3.40%

2.25%

0.17%

Secondary electron distribution

ion)

ION

11.8% -1

EXC

-2

17.6% -3

[2.21 × 10 ]

[6.39 × 10 ]

[4.23 × 10 ]

[3.26 × 10 ]

27.3%

12.6%

12.8%

0.49%

-1

DEA

-2

-1

-1

53.2% -3

[5.13 × 10 ]

[2.37 × 10 ]

[2.42 × 10 ]

[9.19 × 10 ]

0.84%

1.76%

14.5%

12.0%

-2

[1.58 × 10 ]

-2

[3.31 × 10 ]

-1

[2.73 × 10 ]

29.1% -1

[2.26 × 10 ]

Table 1. Spatial probability distributions and collision number distributions of secondary electrons. obtained from the figures 2 and 3 in some spherical regions at 300 fs. The event numbers are presented in parenthesis. The total event number was standardized with respect to the total collision number of 1.88. resulting in DSB induction or complex damage that might compromise the activity of base excision repair enzymes. The diffusible water radicals, such as OH radicals, are not essential for forming the clustered damage site. In the DNA region over 1 nm, most of the secondary electrons would be converted to e-pre during the deceleration process, and the resulting damage, including base lesions, competes with the formation of e-aq (hydration). The base lesions could be easily converted to single-strand breaks by the enzymes, and finally result in the formation of additional DSBs. These results are consistent with our previous experimental evidence for hydrated plasmid DNA exposed to 16


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γ-rays or X-rays19,26-28. Although there were very few diffusible water radicals in the hydrated DNA film, several clustered base lesions (3–4 folds of prompt DSBs) were detected as additional DSBs, which were caused by base excision repair proteins (glycosylases).

■ ACKNOWLEDGMENTS We wish to thank Dr. N. B. Ouchi (QST) and Dr. Y. Hattori (Tokyo Tech) for useful discussions on radiation effects and Prof. Y. Yoshida, Assistant Prof. J. Yang, Dr. T. Kondo, and Dr. K. Kan (Osaka Univ.) for useful discussions on radiation chemistry. This work was supported by JSPS KAKENHI (Grant No. 15H02823).

■ REFERENCES (1) Goodhead, D. T. Initial Events in the Cellular Effects of Ionizing Radiations: Clustered Damage

in DNA. Int. J. Radiat. Bio. 1994, 65, 7-17. (2) Ward, J. F. DNA damage produced by ionizing radiation in mammalian cells: identities,

mechanisms of formation, and reparability. Prog. Nucl. Acid. Res. Mol. Biol. 1988, 35, 95–125. (3) O'Neill, P.; Fielden, E. M. Primary free radical processes in DNA. Advances in Radiation

Biology, 1993, 17, 53-120. (4) Nikjoo, H.; O'Neill, P.; Wilson, W. E.; Goodhead, D. T. Computational approach for determining

the spectrum of DNA damage induced by ionizing radiation. Radiat. Res. 2001, 156, 577-583. (5) Bernhard, W. A.; Close, D. M. DNA damage dictates the biological consequences of ionizing 17



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

radiation: The chemical pathways. In: Mozumder A, Hatano Y, eds. Charged particle and photon interaction with matter. New York: Marcel Dekker, Inc., 2004, 431-470. (6) Nikjoo, H.; Uehara, S.; Emfietzoglou, D.; Cucinotta, F. A. Track-structure codes in radiation

research. Radiation Measurements 2006, 41, 1052-1074. (7) Boudaïffa, B.; Cloutier, P.; Hunting, D.; Huels, M. A.; Sanche, L. Resonant formation of DNA

strand breaks by low-energy (3 to 20 eV) electrons. Science 2000, 287, 1658-1660. (8) Wang, C.-R.; Nguyen, J.; Lu, Q.-B. Bond breaks of nucleotides by dissociative electron transfer

of nonequilibrium prehydrated electrons: a new molecular mechanism for reductive DNA damage. J. Am. Chem. Soc. 2009, 131, 11320–11322. (9) Nguyen, J.; Ma, Y,; Luo, T.; Bristow, R. G.; Jaffray, D. A.; Lu, Q. B. Direct observation of

ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage. Proc.

Natl. Acad. Sci. U S A., 2011, 108, 11778-11783. (10) Kai, T.; Yokoya, A.; Ukai, M.; Fujii, K.; Higuchi, M.; Watanabe, R. Dynamics of low-energy

electrons in liquid water with consideration of Coulomb interaction with positively charged water molecules induced by electron collision. Radiat. Phys. Chem. 2014, 102, 16-22. (11) Kai, T.; Yokoya, A.; Ukai, M.; Watanabe, R. Cross sections, stopping powers, and energy loss

rates for rotational and phonon excitation processes in liquid water by electron impact. Radiat.

Phys. Chem., 2015, 108, 13-17. (12) Kai, T.; Yokoya, A.; Ukai, M.; Fujii, K.; Watanabe, R. Thermal equilibrium and prehydration

processes of electrons injected into liquid water calculated by dynamic Monte Carlo method.

Radiat. Phys. Chem., 2015, 115, 1-5. (13) Bernhardt, Ph.; Paretzke, H.G. Calculation of electron impact ionization cross sections of DNA

using the Deutsch–Märk and Binary–Encounter–Bethe formalisms. Int. J. Mass Spec. 2003,

223–224, 599–611. 18


Page 18 of 20

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(14) Yada, H.; Nagai, M.; Tanaka, K. Origin of the fast relaxation component of water and heavy

water revealed by terahertz time-domain attenuated total reflection spectroscopy. Chem. Phys.

Lett. 2008, 464, 166–170. (15) Wang, C. –R.; Luo, T.; Lu, Q. –B. On the lifetimes and physical nature of incompletely relaxed

electrons in liquid water. Phys. Chem. Chem. Phys. 2008, 10, 4463-4470. (16) Yang, J.; Kan, K.; Kondoh, T.; Yoshida, Y.; Tanimura, K.; Urakawa, J. Femtosecond pulse

radiolysis and femtosecond electron diffraction. Nucl. Instrum. Methods Phys. Res. A 2011, 637, S24–S29. (17) Mozumder, A. Conjecture on electron trapping in liquid water. Radiat. Phys. Chem. 1988, 32,

287-291. (18) Ritchie, R. H.; Hamm, R. N.; and Turner, J. E. Interactions of low energy electrons with

condensed matter: relevance for track structure. In: Varma MN, Chatterjee A (eds) Computational approaches in molecular radiation biology. (Basic Life Sciences 63) Plenum Press, New York, 1994, 33–44. (19) Ushigome, T.; Shikazono, N.; Fujii, K.; Watanabe, R.; Suzuki, M.; Tsuruoka, C.; Tauchi, H.;

Yokoya, A. Yield of single-, double-strand breaks and nucleobase lesions in fully hydrated plasmid DNA films irradiated with high-LET charged particles. Radiat. Res. 2012, 177, 614-627. (20) Prise, K.M.; Pullar, C. H. L.; Michael, B. D. A study of endonuclease III-sensitive sites in

irradiated DNA: detection of alpha-particle-induced oxidative damage. Carcinogenesis 1999, 20, 905-909. (21) Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J. Clustered damages and total lesions

induced in DNA by ionizing radiation: oxidized bases and strand breaks. Biochem. 2000, 39, 8026-8031. (22) Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J. Clustered DNA damages induced in

isolated DNA and in human cells by low doses of ionizing radiation. Proc. Natl. Acad. Sci. U S

A 2000, 97, 103-108. 19



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(23) Blaisdell, J. O.; Harrison, L.; Wallace, S. S. Base excision repair processing of radiation-induced

clustered DNA lesions. Radiat. Protect Dosimetry 2001, 97, 25-31. (24) Sonntag, C. von; The chemical basis of radiation biology, Taylor & Francis, London, 1987. (25) Lu, Q. –B. Effects and applications of ultrashort-lived prehydrated electrons in radiation biology

and radiotherapy of cancer. Mutat. Res. 2010, 704, 190-199. (26) Yokoya, A.; Cunniffe, S. M. T.; O’Neill, P. Effect of hydration on the induction of strand breaks

and base lesions in plasmid DNA films by γ-radiation. J. Am. Chem. Soc. 2002, 124, 8859-8866. (27) Urushibara, A.; Shikazono, N.; O'Neill, P.; Fujii, K.; Wada, S.; Yokoya, A. LET dependence of

the yield of single-, double-strand breaks and base lesions in fully hydrated plasmid DNA films by 4He2+ ion irradiation. Int. J. Radiat. Biol. 2008, 84, 23-33. (28) Shiina, T.; Watanabe, R.; Shiraishi, I.; Suzuki, M.; Sugaya, Y.; Fujii, K.; Yokoya, A. Induction

of DNA damage, including abasic sites, in plasmid DNA by carbon ion and X-ray irradiation.

Radiat. Environ. Biophys. 2013, 52, 99-112.

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Dynamic Behavior of Secondary Electrons in Liquid Water at the

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