Handbook of Radiobiology

Kedar N. Prasad

• Editore: CRC Press
• Anno: 2020
• ISBN:
  9781000141221
• Edizione: 2
• Argomento: Jura
• Categoria: Forensik

This handbook presents the most current information on the effects of ionizing radiation on mammalian cells, with emphasis on human tissues. The dose-effect relationship is emphasized in a quantitative manner. The book contains up-to-date data on the late effects of low levels of radiation on humans. It also provides some of the late consequences of radiation therapy detected among cancer survivors.

Chapter 1

DEVELOPMENT OF RADIOBIOLOGY: A REVIEW

CONTENTS

I. Introduction

II. Major Discoveries in Nuclear Physics

III. Major Discoveries in Biology

IV. Awareness of Hazards and Usefulness of Radiation

V. Agriculture and Food Preservation

VI. Some Major Developments in Radiation Biology

A. Law of Bergonié and Tribondéau

B. Target Theory

C. Indirect Effect

D. Relationship between Chromosome Volume and Radiosensitivity

E. Oxygen Effect

F. Concept of Relative Biological Effectiveness (RBE)

G. Modification of Radiation Damage

H. Quantitative Radiation Biology

I. Cellular Radiosensitivity and Cellular Repair

VII. Summary and Comments

References

I. INTRODUCTION

The development of radiation biology began immediately after the discovery of the X-ray by Roentgen in 1895. Becquerel and Curie observed that certain substances (compounds of uranium, radium, and polonium) were naturally radioactive. Since then, the development of radiation biology has been linked with the advancement of nuclear physics and basic cell biology on the one hand and with the growing awareness of the hazards and usefulness of ionizing radiation on the other. Some of the major discoveries in nuclear physics^16,17,24 and biology^{5,8,20,23,28, 29, 30, 31} that have influenced the growth of radiation biology are briefly described.

II. MAJOR DISCOVERIES IN NUCLEAR PHYSICS

Soon after the discovery of the X-ray and naturally occurring radioactive substances, Thompson defined the physical properties of electrons and protons.¹⁷ In 1911, Rutherford, at the University of Cambridge, discovered alpha-particles, and in 1932 Chadwick made the discovery of neutrons.¹⁷ The availability of neutrons made possible the production of several radioisotopes of biological and medical interest. Also, the relative biologic effectiveness of neutrons with respect to the X-ray was investigated. In 1932, the invention of particle accelerators (the cyclotron) by Lawrence at the University of California, Berkeley, was of great significance.¹⁷ Since then, the cyclotron has been used as a means of production of several radioisotopes of biological and medical interest. Also, the relative biological effectiveness of neutrons with respect to the X-ray was investigated. On December 2, 1942, Fermi and associates at the University of Chicago accomplished a chain reaction from the fission of uranium atoms in a pile of graphite blocks. This remarkable discovery became the basis for manufacturing the atom bomb and the nuclear reactor. Today, most of the radioisotopes of biological and medical interest are produced in the nuclear reactor. In addition to this, the nuclear reactor serves as a source of neutrons of different energies that are being utilized for the study of radiation injuries.

Recent advances in accelerator technology make possible the attainment of very high-intensity proton beams. Such proton beams are adequate for providing pure, high-intensity beams of negative pions (π–). The accelerator, which produces π, is referred to as a “meson factory”²⁴ and is now in use at the Los Alamos Scientific Laboratory, New Mexico. Theoretically, it appears that such a beam could deposit, at essentially any depth in animals and humans, more energy than could be deposited by other particles such as protons, neutrons, and alpha particles. This is due to the fact that when a negative pion is captured by an oxygen nucleus, the mass of the pion is converted into energy with a consequent violent disruption of the oxygen nucleus. From the nucleus emerge neutrons, protons, alpha particles, Li, Be, and C ions; however, the dominant mode involves alpha particles, which have short range. Negative pions can be used in radiobiological studies.

The availability of a variety of radioisotopes has served both as a source of radiation for evaluating the biological hazards of ionizing radiation and as a tracer for the study of the function of various organs and cells.²² It has also helped in providing a better knowledge of the mechanisms of radiation injuries. Radioactive-labeled antibodies are being used in the treatment of human cancers as well as in animal cancer.

Our dosimetry has become accurate;²⁶ therefore, we can establish an accurate dose-effect relationship.

III. MAJOR DISCOVERIES IN BIOLOGY

Several major advances in cellular and molecular biology have markedly influenced the development of radiation biology. For example, the establishment of the mammalian cell line in vitro and the identification of various phases in the life cycle of a cell have increased our understanding of cellular radiosensitivity.⁸ The study of ultrastructures of a cell by an electronic microscope has been very useful in investigating radiation injuries on a subcellular level. Although radiation-induced changes in the ultrastructures of a cell appear nonspecific, these cellular alterations, in combination with biochemical ones, have increased our understanding of radiation injuries. Radiobiologists have not yet taken advantage of the scanning electron microscope, which shows the surface structure of entire cells in great detail.

In 1953, the discovery of the double-helix model of DNA structure had a major impact³⁰ on the development of radiation biology. The structure of DNA and the mechanism of its replication have contributed to our understanding of the mechanisms of radiation damage and repair. The elucidation of protein biosynthesis³⁰ has also increased our knowledge of the mechanisms of radiation damage on the molecular level. The effects of irradiation on biosynthesis and kinetics of nucleic acid and protein synthesis have continued to be studied.

It is now established^19,20 that mitochondria contain DNA that is capable of coding at least certain mitochondrial proteins. This is substantiated by the fact that mitochondria synthesize RNA and protein in vitro. The radiosensitivity of mitochondria has been studied primarily on the basis of morphologic changes, oxidative phosphorylation, and ion transportation, but the effects of irradiation on the biosynthesis of mitochondrial nucleic acid and protein have not been investigated.

Many studies have been performed on the effect of hormones in the regulation of cellular RNA and protein synthesis.^28,29 Several hormones increase enzyme synthesis, which is related to an increased nuclear RNA synthesis. The radiosensitivity of newly formed RNA and protein has not been adequately investigated. Because hormones play an important role in the regulation of the metabolic functions of the cell, such a study would increase our understanding of cellular radiation damage and repair. Studies have established that cyclic nucleotides, adenosine 3′,5′-cyclic monophosphate (cAMP), and guanosine 3′,5′-monophosphate (cGMP) are important for several cellular functions. The importance of cyclic nucleotides in the modification of radiation response has not been adequately studied. These cyclic nucleotides affect the growth, morphology, and differentiation of mammalian cells in culture. The role played by cAMP and cGMP in the radiosensitivity of cells would be important to investigate in order to understand more about the mechanism of radiation damage. In addition, several new growth factors and some new protein kinases have been identified and isolated. The significance of these factors and kinases in modifying the radiation injury has just begun to be studied. The viral oncogenes probes have helped to identify several cellular oncogenes such as c-ras and c-myc. The techniques of molecular biology have been responsible for identifying new cellular protooncogenes. The role of these genes in radiosensitivity has not been studied adequately. The proteolytic activity of RNA under certain experimental conditions was another landmark discovery in biology.

The technique of somatic cell hybridization²³ of two different cell types may prove a very useful tool in obtaining some new insights regarding the radiosensitivity of mammalian cells. Hybrids are produced by fusing two cell types in the presence of an inactivated Sendai virus.

Radiation has contributed directly to the understanding of several aspects of cell biology that would have been difficult to understand by other means. Because radiation is efficient in killing only certain types of cells, the importance of such cells can be more easily evaluated by radiation rather than by other agents such as chemicals, which kill cells nonspecifically. On the basis of this principle, a map of organogenesis has been prepared by irradiating the embryo at different stages of development. Radiation also induces a high incidence of mutation; therefore, it has contributed considerably to our knowledge of mutagenic processes. For example, today we know that mice are much more sensitive to radiation-induced mutation than Drosophila. In addition, the repair of premutational changes occurs in mice.

The use of ³H-thymidine has helped in identifying various phases of the cell cycle and in estimating the period of each phase. The use of other radioactive-labeled compounds as a tracer has increased our understanding of the physiological, biochemical, and metabolical functions of various organs. The use of a lethal dose of X-ra...