Physical events in the track structure of heavy ions and their relation to alterations of biomolecules

Adv. Space Res. Vol. 9. No. 10. pp. (10)15—(10)20. 1989 Printed in Great Britain. All rights reserved.

0273—1177/89 S0.00 + .50 Copyright © 1989 COSPAR

PHYSICAL EVENTS IN THE TRACK STRUCTURE OF HEAVY IONS AND THEIR RELATION TO ALTERATIONS OF BIOMOLECULES H. G. Paretzke GSF—Institut für Strahlenschutz, D-8042 Neuherberg, F. R. G.

ABSTRACT Heavy charged particles Interacting with biological cells can produce a wide variety of different physical, chemical and biological consequences. A rigorous Identification of relevant chemical and biological alterations of biomolecules In cells, however, is still lacking and, thus, it is difficult to identify the potential biological importance of different early physical events. In addition, due to experimental and theoretical problems also little is known about the details of energy transfer, —absorption and -decay from projectiles to atoms/molecules in condensed targets; this is particularly true for not completely stripped heavy ions. Nevertheless, one might conclude from available data that higher densities of physical energy absorption events have a significantly higher probability to lead to qualitatively more severe biochemical alterations as regards the induction of DNA double strand breaks and of chromatin damage. It is not very likely that energy migration along the DNA molecule In biological cells over long distances plays a significant role as contributor to these biological radiation effects. INTRODUCTION The risks to human health of exposure to ionizing radiation need to be quantified in numerous contexts in radiation protection of the general public and of radiation workers. Unfortunately, this quantification of radiation risks cannot be achieved easily from theory nor from analysis of in—vitro experiments. Fortunately, however, these risks can also not be derived from empirical observations in epidemiological studies and animal experiments in the important low dose and low dose rate regime, since there the additional radiation induced cases are hidden in the more numerous and fluctuating spontaneous cases due to the relatively low effectiveness of ionizing radiation on human health. Consequently, attempts have to be made to improve our knowledge on the basic mechanisms of cancer induction and promotion, of genetic mutagenesis and of teratogenesls /1/. This is particularly true for indirect and direct irradiation with heavy Ions. About 2/3 of the human natural exposure, and thus a very large collective dose equivalent is due to alpha-particles from radon and thoron decay products /2/; there is increased concern about the magnitude of radiation risks from occupational and medical neutron exposure (leading to energetic heavy ions in the human body), and a small number of people will become directly exposed to fast heavy ions during space flights and in cancer therapy treatments. For such heavy ions, there is only an extremely limited epideniiological and experimental data base from which associated health risks can be estimated. Therefore mechanistic research into the biological effects of heavy ions Is of particular interest. This paper discusses, first, some aspects of physical events in the tracks of such ions and then tries to assess their potential Importance for radiolytic alterations of biomolecules. PHYSICAL EVENTS OF HEAVY IONS Fast charged particles loose their energy upon penetration through matter mainly through excitations and ionisatlons; quasi—elastic Coulombic collisions occur too infrequent to be of significance in radiation risk analysis. Heavy ions with specific energies from, say, 0.5-100 MeV/u transfer about 70 % of their energy loss into kinetic energies of electrons ejected from the atomic shells of the target atoms, about 20 % is needed to overcome the binding potential of these “secondary elelctrons” and only the residual 10 % of the energy loss dE/dx /3/ produces neutral excited species. This large fraction transferred and transported by secondary electrons emphasized the large importance for radiation research of understanding the radiation action of electrons also in this context; the dominance of Comp— ton— and photoelectrons in determining the actions of X-rays and gammaquanta is self—evi— (10)15

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H. G. Paretzke

dent. The energy spectra of secondary electrons produced by protons in gases have been measured extensively ~4-6/.At low secondary electron energies the differeQtial cross section de— creases ~ T lnT, at medium and high energies approximately ~ T’, where T2is the the maximum proton energy. cross section at medium electron linearly energies with E roughly E secondaryTheelectron energy falls increases approximately 1. The asangular distribution of these electrons is generally rather isotropic for the numerous low energy electrons and shows with increasing electron energy a classical binary encounter peak at kinematically appropriate angles (see Figure 1). Unfortunately, the problems with these important cross sections start already with the first electron bound to the projectile (Figure 2), here a H 2—molecule /8/. Here clearly the electron contribution to these spectra from the projectile at the projectile velocity can be seen. Also the experimental data for He+ and H°impact show similar structure due to projectile electrons. Our present quantitative understanding of these spectra, however, is far from being satisfactory. This situation is worse for heavier ions with more own electrons and, thus, showing even more structure and an increasing likelihood of multiple ionizations

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Track Structure of Heavy Ions

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in one single interaction /9/. It has been proposed /10/ to use the effective ion charge Z~ as derived from range measurements /11/ to scale proton cross sections to those for heavier ions. However, it is evident that by this method the electrons from the projectile cannot be accounted for since an incoming proton has none of these. Furtheron, the few available data for heavier impinging ions /12—14/ clearly demonstrate the significant effect of shielding in distant collisions (leading to slow secondary electrons) as compared to close collisions (leading to high energy secondaries), i.e. the projectile has different “effective charge states’ for different parts of a secondary electron spectrum. This fact and the changing multiplicity of lonisations per collision /9,15/ make the theoretical or experimental derivation of secondary electron spectra of heavy ions a rather difficult task even for gaseous targets. The state of knowledge for condensed targets is even worse because of the unknown, but highly excited state of the projectile before a certain energy loss event and, second, because of the non—availability of the ejected electrons for analyses before subsequent moderating collisions. Inspite of these impoçtant shortcomings, in general the density of events will increase approximately with (Z /13)2, where 13 is the ion velocity relative to the speed o.f light. The 2-dependency can clearly be seen in Figure 3 showing a two—dimensional representation of 13 the locations of ionizations in computer generated proton tracks in water (vapor) /16/. The increase in event density leading to an increase of the likelihood of subsequent reactions among new chemical species with decreasing ion velocity can clearly be seen. —

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Fig. 3. Computer simulated tracks of 0.3, 1, and 3 MeV protons in water (vapour) (from /16/). Not to be seen is, for statistical reasons, the increasing radial extension of heavy ion tracks with increasing ion energy. Figure 4 shows this effect in a low—Z model substance, ngmely the scaled mean radial energy deposition density for fast ions of “effective” charge Zeff /11/, Energy E, Mass M, as a function of the track radius. At small radii most of the energy deposition stems from the ejected weakly bound Outer target electrons; at large radii also these secondary electrons have essential contributions proportional to their relative number in the target atom, which were bound in inner shells. It should be pointed out that such average energy densities have some meaning for radiation biology only if subsequent chemical and biological reactions do not depend on the local energy density with a higher power than one. Biomolecules, however, will always react according to actually experienced disturbances and not necessarily on expectation values of such distributions.

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H. 0. Paretzke

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Mean scaled radial energy deposition density for fast ions of 0.1, 0.25, 0.5, 1,

5, and 10 MeV/u energy as a function of radius. RELEVANCY OF EVENTS FOR BIOMOLECULES The DNA has been suspected for a long time to be the critical molecular target in which radiation induced alterations can have severe biological /17—19/ implications. In principle, many alterations of the DNA, as e.g. base damage, single strand breaks, double strand breaks, alkali—labile sites and combinations thereof, could have deleterious effects on it. However, many experimental data indicate that — at least regarding lethality — unrepaired double strand breaks might play a particular important role /20—22/. Such double strand breaks might very well be “dirty” (and, thus, more difficult to be repaired properly) in high—energy density events as they are preferentially produced by heavy ions. Here the proposed mechanism of the “Coulomb explosion” of atoms in a molecule highly ionized could have a particular importance /23/. High energy density events in ion tracks (E)100 eV) but also tracks of electrons with energies between, say, 200 and 2000 eV energy could play a prominent role in radiation biology /24,25/. Such densities of events are high enough to lead potentially even to severe chroma— tin damage by direct and indirect action. A distinction between these two modes of action, however, does not make much sense for eukaryotic cells. Here the DNA is tightly bound to histones, the water molecules in the DNA hydration shell have quite different diffusion, etc. properties as compared to ordinary water /26/ (it could even not be capable to solvate electrons /27/), and also the high other organic material content of the cell nucleus restricts the potential diffusion distances of relevant radicals (e.g. 0H~—radicals) to one or two nanometers /17/. Therefore most of the effective events must be located directly on the DNA-molecule or in the immediate neighbourhood (< 2 nm). When energy is lost from a passing fast heavy ion these energy quanta need not be absorbed immediately by a target molecule but it might become delocalized either because of the validity of the Heisenberg uncertainty principle or because of the excitation of a plasmon type collective excitation (of up to 10~electrons) /28,29/. The latter can occur even within one single molecule (e.g. in it—electron states). The coupling ~o one (or more) electrons of such a delocalized state will occur within less than about 10-1 s and the spatial displacement can be up to more than 10 nm /30/. However, the amount of energy transferred is the plasmon state energy of typically 25 eV or even only 3-6 eV (,t-electron states). Therefore it cannot be expected that this delocaljzatjon mechanism can transport those large energy quanta needed to cause severe damage as mentioned above. Similar considerations apply to the relevance of the postulated soliton, exciton or polaron energy transfer mechnism along DNA /31/. Here also the maximum distance, along which energy quanta (below 25 eV) can be transported, will be shorter in intracellular DNA because of structural traps. In summary, the state of knowledge on relevant physical events at early times after interaction of heavy ions with biomulecules in cells as well as on the resulting biochemical alterations, their repair and final relevancy is still far from being satisfactory. The aim of understanding biological radiation action well enough to be able to base risk estimates at low doses and dose rates on such theoretical considerations remains an important and interesting open problem.

Track Structure of Heavy Ions

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REFERENCES

1.

W.K. Sinclair and R.J.M. Fry, Radiat. Res. 112, 407 (1987).

2. 3.

National Council on Radiation Protection and Measurements, Ionizing Radiation Exposure of the Population of the United States, Report No. 93, Bethesda, USA, 1987. J.F. Ziegler, The Stopping and Range of Ions in Matter, Pergamon Press, N.Y., 1978.

4.

L.H. Toburen and W.B. Wilson, 3. Chem. Phys. 60, 5202 (1977).

5.

M.E, Rudd, Y.—K. Kim, D.H. Madison, and J.W. Gallagher, Rev. Mod. Phys. 57 (1985).

6.

M.E. Rudd, L.H. Toburen, and N. Stolterfoht, At. Data Nucl. Data Tabl. 23, 405 (1979).

7.

W.E. Wilson and H.G. Paretzke, Electron Ejection Cross Sections, in: Fourth Symp. on Microdosimetry, ed. J. Booz, H.G. Ebert, R. Eickel, and A. Waker, EUR—Report ~12, Commission of the European Communities, Luxembourg, 1974, p. 113.

8.

W.E. Wilson and L.H. Toburen, Phys. Rev. A7, 1535 (1973).

9.

H.D. Betz, Rev. Mod. Phys. 44, 465 (1972).

10.

R. Katz and

11.

W,F. Barkas, Nuclear Research Emulsions, Academic Press, N.Y., 1963.

12.

P.H. Woerlee, Y.S. Gordeev, H.de Waard, and F.W. Saris, J. Phys. B 14, 527 (1981).

13.

L,H. Toburen, N. Stolterfoht, P. Ziem, and D. Schneider, Phys. Rev. A 24, 1741. (1981).

14.

R.D. BuBois, Phys. Rev. A 36, 2585 (1987).

15.

W.G. Graham, K.H. Berkner, R.V. Pyle, A.S. Schachtner, D.W. Sterus, and J.A. Tanis,

E.J.

Kobetich, Mud. Instr. Meth. 79, 320 (1970).

Phys. Rev. A 30, 722 (1984). 16.

H.G. Paretzke, Radiation Track Structure Theory, in: Kinetics of Nonhomogeneous Processes, ed. G.R. Freeman, Wiley—Interscience, N.Y., p. 89. 1987.

17.

C. von Sonntag, The Chemical Basis of Radiation Biology, Taylor & Francis, London, 1987.

18.

L.K. Mee, Radiation Chemistry of Biopolymers, in: Radiation Chemistry Principles and Applications, ed. Farhataziz and M.A.J. Rodgers, VCH Verlagsgesellschaft, Weinheim, p. 477, 1987.

19.

J.E.

Braglow, The Effects of Ionizing Radiation on Mammalian Cells, ibid., p. 527.

20.

J.F.

Ward, Radiat. Res. 104, 103 (1985).

21.

0. Frankenberg, M. Frankenberg—Schwager, U. Bl~cher, and R. Harbich, Radiat. Res. 88, 524 (1981).

—

22. H.P. Leenhouts and K.H. Chadwick, Adv. Radiat. Biol. 7, 55 (1978). 23, R.L. Fleischer, P.B. Price, and g.M. Walker, J. Appl. Phys. 36, 3645 (1965). 24. H.G. Paretzke, An Appraisal of the Relative Importance of Effects of Slow Electrons, in: Fifth S~~mp.on Nicrodosimetry, ed. 3. Booz, H.G. Ebert, and B.G.R. Smith, EUR—Report 5452, Comission of the European Communities, Luxembourg, p. 41, 1976. 25. D.T. 000dhead and H. Nikjoo, Track Structure Analysis of Ultrasoft X-rays compared to High— and Low— LET Radiations, submitted to I. J. Radiat. Biol. (1988). 26. G. Ebert, Biopolymere, Steinkopf, Darmstadt, p. 14. 1980. 27. D. van Lith, J.M. Warniann, M.P. 82, 2933 (1986). 28.

de Haas, and A.

Hummel, J. Chem. Soc. Faraday Trans.

U. Fano, Phys. Rev. 118, 451 (1960).

29. H. Raether, Excitation of Plasmons and Interband Transitions by Electrons, Springer Tracts in Modern Physics, Springer—Verlag, Berlin, Vol. 88, 1980.

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H. 0. Paretzke

30.

I.G. Kaplan and A.M. Miterev, Interaction of Charged Particles with Molecular Medium

31.

K.F. Baverstock and R.B. Cundall, Nature 322, 312 (1988).

and Track Effects in Radiation Chemistry, Adv. Chem. Phys. 68, 255 (1987).