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Über dieses Buch

The biological action of radiation undoubtedly constitutes an issue of actual con­ cern, particularly after incidences like those in Harrisburg or Chernobyl. These considerations, however, were not the reason for writing this book although it is hoped that it will also be helpful in this respect. The interaction of radiation with biological systems is such an interesting research objective that to my mind no special justification is needed to pursue these problems. The combination of physics, chemistry and biology presents on one hand a fascinating challenge to the student, on the other, it may lead to insights which are not possible if the dif­ ferent subjects remain clearly separated. Special problems of radiation biology have quite often led to new approaches in physics (or vice versa), a recent example is "microdosimetry" (chapter 4). Biological radiation a9tion comprises all levels of biological organization. It starts with the absorption in essential atoms and molecules and ends with the development of cancer and genetic hazards to future generations. The structure of the book reflects this. Beginning with physical and chemical fundamentals, it then turns to a description of chemical and subcellular systems. Cellular effects form a large part since they are the basis for understanding all further responses. Reactions of the whole organism, concentrating on mammals and especially humans, are subsequently treated. The book concludes with a short discussion of problems in radiation protection and the application of radiation in medical therapy. These last points are necessarily short and somewhat superficial.

Inhaltsverzeichnis

Frontmatter

Chapter 1. Types of Radiation: Characterization and Sources

Abstract
This introductory chapter gives a description of the different types of radiation and briefly outlines the means of their production. Spectral distributions are explained and discussed. A final paragraph deals with the fundamentals of radioactivity.
Jürgen Kiefer

Chapter 2. Fundamentals of Radiation Attenuation in Matter

Abstract
It is the aim of this chapter to introduce the fundamental properties and mechanisms governing the interaction of radiation and matter. This is to provide the basis for more detailed considerations in the following chapters. The important concept of “interaction cross section” is explained and discussed followed by the formalisms of collision processes, both with and without the action of an attracting field. This allows to derive expressions for the amount of energy transferred.
Jürgen Kiefer

Chapter 3. Interaction Processes

Abstract
Based on Chap. 2, the most important interaction processes for understanding biological radiation effects are described and treated quantitatively. Charged particles are particularly emphasized since they play an essential role in the effects of ionizing radiation. This also involves fundamental approaches for the determination of ranges and fluence distributions.
Jürgen Kiefer

Chapter 4. Deposition of Radiation Energy

Abstract
Energy transfer by radiation to biological systems is both of fundamental and practical importance. The central quantity with ionizing radiation is the dose (absorbed energy per unit mass); However, there is a difference between energy transferred and energy deposited, as will be explained in detail. The spatial distribution of absorption events also plays a significant role which is macroscopically described by the “linear energy transfer” (LET). The applicability of this concept is critically discussed. In microscopical dimensions the stochastic nature of energy absorption events becomes important, an issue which is dealt with under the heading “microdosimetry”. This will be followed by a description of the energy deposition in the close vicinity of the track of an ionizing particle. The concept of dose as defined above is generally not meaningful with optical radiation; thus, other relevant quantities such as photon or energy fluence are introduced.
Jürgen Kiefer

Chapter 5. Elements of Photo- and Radiation Chemistry

Abstract
This chapter focuses on the basic features of photo- and radiation-chemical reactions as far as they are relevant for the understanding of biological processes. These include the basic mechanisms of photosensitization and of action spectroscopy which allows to identify the primary absorber in a biological effect by studying its wavelength dependence. More specifically, atmospheric photochemical reactions and the light-dependent formation of vitamin D are discussed. The decomposition of water is described and, particular attention is paid to the influence of oxygen and different ionization densities, providing the background for the understanding of cellular phenomena. The chapter concludes with a discussion of direct and indirect radiation effects.
Jürgen Kiefer

Chapter 6. Photo- and Radiation Chemistry of DNA

Abstract
Radiation-induced alterations of DNA are summarized. The pyrimidine dimer is still considered to be the major photoproduct. With ionizing radiation, such an exclusive statement is not possible although strand-breaks undoubtedly play a very important role. The influence of exposure conditions and modification by additives (photosensitizers, oxygen) are described as well as the dependence on ionization density.
Jürgen Kiefer

Chapter 7. Radiation Effects on Subcellular Systems

Abstract
Radiation effects on enzymes and viruses are discussed along with the inhibition of RNA transcription. First, an introduction of “target theory” will be given which describes quantitatively the effects on “small” systems. Investigations using viruses (especially bacteriophages), plasmids or isolated DNA are outlined. A special section deals with repair phenomena at the subcellular level. The chapter includes also a description of “gene mapping”, which demonstrates how radiobiological approaches may be successfully applied to problems of general molecular biology.
Jürgen Kiefer

Chapter 8. Loss of Reproductive Ability in Cells

Abstract
Cell survival, in radiobiological terms, is understood as the ability for indefinite reproduction. After a description of basic techniques, the formalism of survival curves is discussed. The next section shows whether and how the different sensitivities of cell species may be interpreted; it will be shown that it is related — at least with ionizing radiation — to the amount of genetic material. A description of the influence of radiation quality is followed by a consideration of action spectroscopy with UV and the importance of the spatial pattern of energy deposition with ionizing radiation. The concept of “relative biological effectiveness” (RBE) is introduced and critically discussed. The chapter concludes with a discussion of the interaction of different radiation types in combination experiments.
Jürgen Kiefer

Chapter 9. Radiosensitization and Protection

Abstract
Recent developments in photosensitization are discussed along with substances having a certain relevance in medical treatment. The mechanisms of protection and sensitization with ionizing radiation are dealt with in greater depth, particularly the “oxygen effect”; hypotheses for its interpretation are discussed. Radiosensitization by chemical agents, especially those with a possible clinical potential, will be discussed by end of the chapter.
Jürgen Kiefer

Chapter 10. Radiation and the Cell Cycle

Abstract
Radiation sensitivity (expressed as loss of colony forming ability or mutability) depends on the cell cycle stage in which the cells are exposed. This is found both with UV and with sparsely ionizing radiations; in many cases, the two types show a mirror-image-like relationship. Radiation also slows down the progression of cells through the cycle; this effect is reversible with low doses. The inhibition of DNA synthesis is particularly relevant in this respect and will, therefore, be discussed in more detail.
Jürgen Kiefer

Chapter 11. Chromosome Aberrations

Abstract
This chapter deals with cytological alterations. Chromosome aberrations are particularly important because they can be detected already in the first post-exposure cell division and allow, therefore, a closer insight into basic mechanisms. Furthermore, they lead to genetic diseases and constitute also an important tool in practical radiation hazard evaluation.
Jürgen Kiefer

Chapter 12. Mutation and Transformation

Abstract
This chapter deals with genetic alterations at the cellular level. At the beginning the general fundamental questions and techniques are discussed followed by an outline of experiments in bacteria where the relation to repair processes is well understood. Investigations with mammalian cells are treated in more detail (dependence of radiation quality and cell cycle stages etc). A comparison of different systems shows that mutation frequencies per unit dose increases with DNA content which has consequences for the interpretation of mechanisms. The very important technique of in vitro neoplastic transformation and some results obtained are introduced in the last section.
Jürgen Kiefer

Chapter 13. Repair and Recovery

Abstract
A distinction is made in this chapter between “repair” and “recovery”. The first includes only those processes where the molecular mechanism is fairly well known. Examples are photoreactivation, excision, post replicational repair, mismatch repair, “SOS”- and strand-break repair. “Recovery”, on the other hand, is operationally defined as a phenomenon which reduces the cellular radiation effect without specific reference to a certain process at the molecular level. The last section discusses the genetic dependence of repair processes and also their relevance for human health.
Jürgen Kiefer

Chapter 14. Modifications of Radiation Effects by External Influences

Abstract
It is the aim of this chapter to demonstrate with a few important and typical examples how the biological radiation effect may be modulated by external parameters, apart from those which were already treated in more detail. The time pattern of exposure plays an important role, both fundamentally and practically. With respect to the recent interest in hyperthermia in radiation therapy, the combination of heat and radiation at the cellular level is discussed. Modifications by pharmaceutical agents can only be described by a few examples, mainly repair inhibitors. The last section deals with changes in tonicity to demonstrate the complexity of biological radiation action and may serve as a safeguard to avoid the premature acceptance of too simple mechanistic models.
Jürgen Kiefer

Chapter 15. Special Aspects of Cellular Radiation Action

Abstract
In this chapter some questions are addressed which are felt to be sufficiently relevant to deserve mentioning but were difficult to incorporate elsewhere. The action of long-wavelength UV and visible light is certainly important from an ecological point of view but also with regard to some medical applications. Radiowaves and ultrasound are also becoming to play a role in diagnosis and sometimes therapy, and there is some concern in the public about possible hazards. Chemicals which act similar to radiation — radiomimetics — have their place in chemotherapy but may also be relevant in terms of general toxicology. The importance of radionuclide incorporation needs no justification but it is also shown that they are interesting tools to learn more about site and mode of cellular radiation action.
Jürgen Kiefer

Chapter 16. Theoretical Models of Cellular Radiation Action

Abstract
This chapter describes some of the theoretical approaches to describe quantitatively the action of radiation on cells. The aim of these attempts is not predominantly to bring radiation biology from a descriptive to a higher theoretical level but more to allow estimates in dose ranges where direct experimental determinations are not feasible or even possible. A well known and important example is the behaviour at very low doses and dose rates. All models may be roughly grouped into two categories: in the first, the emphasis is laid on the distribution of initial lesions and their interactions, while in the second, repair and its efficiency are the focal points. Examples of both types are given.
Jürgen Kiefer

Chapter 17. Cell Survival in Relation to Whole Body Effects

Abstract
The relevance of cell division for the function of the whole organism is discussed, and the basic structure of some systems outlined. This is followed by the description of some techniques which allow the determination of cell survival in vivo together with a review of important results.
Jürgen Kiefer

Chapter 18. Acute Radiation Damage

Abstract
Acute radiation reactions in special organs or systems (skin, eye, immune system) are treated first, both with UV and ionizing radiation. The main part of the chapter is devoted to the acute radiation syndrome as it develops after whole-body exposure to ionizing radiation and which is mainly caused by the impairment of cell division in the renewal systems of the blood-forming organs and the alimentary tract. In the last section, the acute “radiation sickness” in its clinical form is briefly described.
Jürgen Kiefer

Chapter 19. Radiation Effects and Progeny

Abstract
This chapter summarizes all the effects which influence — either directly or indirectly — the children of the exposed individual. These are disturbances of fertility, intrauterine death, teratogenesis and genetic changes. The experimental methods for hazard assessment are introduced and the basis for risk estimates discussed.
Jürgen Kiefer

Chapter 20. Late Somatic Effects

Abstract
This chapter deals with those biological consequences in the mammalian organism which show up long times after a radiation insult. The eye reacts rather sensitively in this respect by cataract formation. This is an important example of late effects other than cancer. Radiation-induced tumours form, of course, the most important class. They are also related to radiation-induced life shortening, as discussed in some detail. The ways and means of tumour risk assessment are described.
Jürgen Kiefer

Chapter. Effects of Internal Exposure

Abstract
The incorporation of radionuclides plays an important role in the assessment of radiation risks. The basic considerations, the ways of incorporation and the principles of computational methods are introduced. Incorporation may take place either by breathing (“inhalation”) or eating or drinking (“ingestion”). For the estimation of the radiation load it is necessary to distinguish between the deposition organs which may — apart from being exposed themselves — act as radiation sources from which other parts of the body (“target organs”) may be irradiated. The calculations lead to the recommendation of ‘annual limits of intake’ for which examples are given.
Jürgen Kiefer

Chapter 22. Radioecology

Abstract
This chapter deals with radiation in the environment. The treatment requires a systematic approach whose fundamental principles are outlined. Because of Me manifold interrelations it becomes necessary to use simplifying models and calculational methods. Specifically, possible changes in the solar spectrum due to atmospheric reactions are described as well as natural and anthropogenic sources of ionizing radiation. The distribution of radioactivity with particular emphasis on the food chain is discussed laying thus the basis for realistic risk estimates.
Jürgen Kiefer

Chapter 23. Principles of Radiation Protection Regulations

Abstract
It is the aim of this chapter to give a certain insight into the considerations which lead to recommendations for radiation protection and which form the body of most national and supra-national regulations. The relevant new quantities and units are introduced and discussed.
Jürgen Kiefer

Chapter 24. Radiobiology in Radiation Therapy

Abstract
Radiobiological experience may influence radiotherapeutical practice and lead to new modalities. The treatment of the topic can only be exemplary in nature and cannot be comprehensive. Phototherapy is mainly applied with certain nonmalignant skin diseases but it is recently extended also to non-skin cancers. Ionizing radiation is widely used in cancer treatment. Experimental model systems are described which were designed to understand the underlying principles and to test possible new developments. A few such examples are discussed: namely new types of radiation, particularly those with better depth dose distributions, the combination with hyperthermia or the concomitant application of chemical agents.
Jürgen Kiefer

Backmatter

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