Lett / Sinclair DNA and Chromatin Damage Caused by Radiation

1. Auflage 2013
ISBN: 978-1-4832-8227-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 516 Seiten

Advances in Radiation Biology, Volume 17: DNA and Chromatin Damage Caused by Radiation outlines the different biological reactions to radiation. This book discusses the linear energy transfer and energy loss; DNA breaks and track structure; DNA radicals from water radicals; and radiation-induced strand breaks in isolated DNA. The radiation damage to DNA and its nearby environment; thiol radioprotectors and mechanism of action; radiolysis of water and track reactions; and computer simulation of higher order structure of DNA are also elaborated. This publication likewise covers the concept of chromatin structure; DNA supercoiling studied by sedimentation; measurement of radiation-induced DNA breakage; and analysis of damage in interphase cells. This volume is a useful reference to biologists and students concerned with DNA and chromatin damage caused by radiation.

Autoren/Hrsg.

Lett, John T.

Sinclair, Warren K.

Inhaltsverzeichnis

1;Front Cover;1
2;DNA and Chromatin Damage Caused by Radiation;4
3;Copyright Page;5
4;Table of Contents;6
5;Chapter 1. Linear Energy Transfer and Track Structure;10
5.1;I. Introduction;10
5.2;II. Linear Energy Transfer and Energy Loss;14
5.3;III. d-Electron Emission;25
5.4;IV. Condensed Phase Effects—Track Core;31
5.5;V. Electron Transport and the Track Halo;36
5.6;VI. DNA Breaks and Track Structure;49
5.7;VII. Summary;54
5.8;References;58
6;Chapter 2. Primary Free Radical Processes in DNA;62
6.1;I. Introduction;62
6.2;II. DNA Radicals from Water Radicals—Recent Advances;69
6.3;III. One-Electron Oxidized Species of DNA in an Aqueous Environment;88
6.4;IV. Dynamics of Radiation-Induced Changes in Solid DNA;101
6.5;V. Radiation-Induced Strand Breaks in Isolated DNA;114
6.6;VI. Forward Look;121
6.7;References;123
7;Chapter 3. The Chemical Consequences of Radiation Damage to DNA;130
7.1;I. Introduction;130
7.2;II. Radiation Damage to DNA and Its Nearby Environment: Direct and Quasi-direct Effects;144
7.3;III. The Indirect Effect;160
7.4;IV. The Confluence of Chemical Events for the Direct, Quasi-direct, and Indirect Effects;174
7.5;V. Thiol Radioprotectors and Mechanism of Action;175
7.6;VI. Conclusions and Directions for Future Efforts;181
7.7;References;182
8;Chapter 4. Computer Simulation of Initial Events in the Biochemical Mechanisms of DNA Damage;190
8.1;I. Introduction;190
8.2;II. Energy Deposition Events and Creation of Tracks by Charged Particles;192
8.3;III. Radiolysis of Water and Track Reactions;199
8.4;IV. Computer Simulation of the Biochemical Stage: The Formation of Strand Breaks;209
8.5;V. Results of Yields on Strand Breaks;222
8.6;VI. Computer Simulation of Higher Order Structure of DNA;230
8.7;VII. Concluding Remarks and Future Directions;233
8.8;References;236
9;Chapter 5. DNA Loop Structure and Radiation Response;238
9.1;I. Introduction;238
9.2;II. The Concept of Chromatin Structure;239
9.3;III. DNA Supercoiling Studied by Sedimentation;242
9.4;IV. Alternative Methods;246
9.5;V. DNA Loop Structure and Growth State;251
9.6;VI. DNA Loop Structure, Anchoring, and Radiosensitivity;253
9.7;VII. Cell Cycle Effects;263
9.8;VIII. Conclusions;267
9.9;References;267
10;Chapter 6. Radiation-Induced Damage in Chromosomal DNA Molecules: Deduction of Chromosomal DNA Organization from the Hydrodynamic Data Used to Measure DNA Double-Strand Breaks and from Stereo Electron Microscopic Observations;272
10.1;I. Introduction;272
10.2;II. Methods for the Measurement of DNA Breakage;275
10.3;III. DNA Size, Shape, and Number Concentration Measurement;277
10.4;IV. Problems Unique to the Measurement of Large DNA Molecules;303
10.5;V. Measurement of Radiation-Induced DNA Breakage;308
10.6;VI. Size and Shape Determination of Mammalian Cell Chromosomal DNA Molecules;315
10.7;VII. Structure of the Mammalian Chromosome;321
10.8;VIII. Summary;423
10.9;References;425
11;Chapter 7. Ionizing Radiation Damage and Its Early Development in Chromosomes;434
11.1;I. Introduction;434
11.2;II. Chromosomal Aberrations at Mitosis;436
11.3;III. Analysis of Damage in Interphase Cells;460
11.4;IV. What Are PCC Breaks?;478
11.5;V. The Nature of Critical Cellular Structures;485
11.6;VI. Conclusions;490
11.7;References;502
12;Index;510

Leseproben

1

Linear Energy Transfer and Track Structure

Gerhard Kraft and Michael KrÄMer,     Gesellschaft Für Schwerionenforschung mbH, D-6100, Darmstadt, Germany

Publisher Summary

This chapter discusses track structures and linear energy transfer. There are two types of energy dissipation of heavy ions—nuclear and electronic stopping. Nuclear stopping has high RBE values and predominates at extremely low specific energies of a few kiloelectronvolts per mass unit, corresponding to the last micrometers of the particle range. At higher energies, nuclear stopping contributes only a few percent to the total stopping; the predominant process is the electronic stopping. The electronic stopping is proportional to the square of the effective projectile charge and increases up to a maximum value. The predominant process of electronic stopping involves the interaction of the projectile with the target electrons. In the collision process, a spectrum of electrons is produced with different kinetic energies ranging from zero up to a maximum energy that depends on the velocity of the primary ion. From the energy loss of the primary ion, two-thirds are transformed into the kinetic energy of the electrons. The residual energy is used to overcome the binding energy of the electrons and for target excitations. In the center of the track, the ionized atoms are pushed out from their original positions by electrostatic repulsion. This process is called Coulomb explosion and is responsible for the formation of the latent track in nuclear track detectors. In DNA experiments, the influence of track structure on the induction of double- and single-strand breaks is observed for LET values greater than 5 keV/µm. In consequence, the ratio of DSB to SSB increases with decreasing track diameters, and the highest values are found at the very end of the tracks. However, if the radiosensitivity is increased by changing the DNA environment or the repair capacity, additional DSB are produced directly in single events.

I Introduction

Dose is currently regarded as the principal parameter in radiobiology. Usually, the different biological reactions to ionizing radiation are studied as a function of dose. From a comparison of the dose–effect curves, conclusions concerning the basic mechanism governing the radiobiological reactions are drawn. From its definition as energy deposited per mass unit, dose appears to be a “continuous” parameter and it should be possible to divide it into infinitesimal subunits of smaller mass elements receiving smaller amounts of energy. As it turns out, this is not true even for relatively large objects like subcellular structures where the size of the target exceeds the atomic dimensions by many orders of magnitude.

For sparsely ionizing radiation like X- or ?-rays, the energy is transferred from the electromagnetic radiation via Compton or photo processes or pair production into more or less energetic electrons. It is not only these processes but also the secondary collision processes of the liberated electrons that result in ionization and consequently in biochemical and biological damage. With electrons as the primary radiation, the biochemical and biological effects are produced by the ionization processes of these electrons and their subsequent electron cascade.

When masses or volumes containing only a few or one electron are considered, the “grainy structure” of dose becomes visible. Microdosímetry has demonstrated that for small volumes of tissue-equivalent materials this fine structure of the energy deposition plays an important role (Kellerer and Rossi, 1978).

In general, the radiobiological effect of all types of sparsely ionizing radiation are caused by the action of liberated electrons and of the primary ionization events. With the exception of very low energy electrons produced, for example, by soft X-rays, the liberated electrons experience the same slowing down process in the target. In consequence, the biological efficiency differs only some 10% between electromagnetic radiation produced from different sources like Co-?-rays or the Bremsstrahlung spectrum of an X-ray tube.

For particle radiation like protons, a-particles, or heavier ions (and also for neutrons, which act via reaction and recoil ions), a much larger variation in the relative biological efficiency (RBE) is observed. Their biological effect is caused by primary ionizations occurring along the particle trajectories and the action of the liberated electrons and their secondaries. Differences in the biological efficiency of these particles therefore have to be attributed to the spatial and time correlations of the ionization events caused by the electrons and the primary particle.

In radiobiology different concepts are used to characterize radiation quality: the LET concept, the track structure concept, and the concept of microdosimetry.

In early studies of particle radiobiology, the specific ionization density, i.e., the number of ion–electron pairs created along the path of the particle, was used to characterize densely ionizing radiation. But assuming that for the creation of each ion–electron pair the same constant amount of energy is necessary, the number of ionization events per track follows exactly the electronic stopping power curve in its dependence on particle energy. For gases it is known that on the average an energy of approximately 31 eV is necessary to create an ionization event, but for material of tissue density, this quantity is not known. Therefore, Zirkle proposed in 1954 to characterize densely ionizing radiation by the linear energy transfer (LET) to the absorber material. The LET measured in kiloelectronvolts per micrometer is numerically identical with the stopping power of the particles in water as reference material as long as no restrictions to the d-electron1 energy are applied.

Linear energy transfer has proven to be a useful parameter in the description of many radiobiological effects in different cellular and subcellular targets. In general, the RBE increases with increasing LET values up to a maximum at around 100 keV/µm. At higher LET values, RBE decreases to values much smaller than one (Barendsen ., 1963). Exceptions from this general behavior are the induction of single-strand breaks and other biological effects related to single-strand breaks, but not to double-strand breaks (Kraft, 1988). In addition, radiation effects in very sensitive targets, for instance, in repair-deficient mutants (Lett ., 1989), where the track structure seems to play only a minor role, do not show RBE maxima at LET values around 100 keV/µm. However, the same steep decrease of RBE for higher values of LET is also found for these effects.

In the last decade it has been shown experimentally that LET is not a good parameter when different ions, having different atomic numbers, are used (Todd, 1965; Wulf ., 1985; Kraft, 1987; Belli ., 1989; Folkard ., 1989). In this case, for the same LET, different biological efficiencies have been observed. In addition, it was also evident from atomic and nuclear track physics that LET cannot be a good parameter to describe the action of heavy charged particles independently from the particular particle species.

From atomic physics it is known that the energy loss of the primary particle is not simply divided into very small packages just creating ion–electron pairs like pearls on a string. The µ-electrons are ejected with a spectrum of kinetic energies (Bethe, 1930) and can cause further ionization at reasonable distances from the primary track (Kobetich and Katz, 1968a). This was confirmed by the observation in nuclear track physics of extended tracks of several micrometer in diameter recorded in nuclear photo emulsions after their exposure to highly energetic particles from cosmic rays or from accelerators (Kobetich and Katz, 1968b). The diameter of these tracks can be much larger than the dimensions of critical structures inside cells or even larger than a complete cell. In consequence, the three-dimensional distribution of ionization events around the particle track and the effects of the elevated ionization density must be known for a complete description of radiation effects of particles. Up to now, this has not been achieved.

There are two reasons for this failure. First, the collision process between the projectile and the target atom with its electron is not understood in detail; i.e., the energy and the angular dependence of the emitted d-electrons has not been measured for heavy ion impacts on solid targets and only a few measurements for gas targets exist. Therefore, it is not known precisely how the primary ionizations events are formed along the particle track and what fraction of the energy is transported via the electrons outside the primary collision region. Second, the fate of the emitted electrons is also not known. These d-electrons are scattered both elastically without significant energy loss but changing direction and inelastically creating new ionization events or excitations. Even very sophisticated Monte Carlo calculations (Paretzke, 1988) of track structure use mostly simplified...