Molecular Radiation Biology: The Action of Ionizing Radiation on Elementary Biological Objects

246 Pages·1970·10.33 MB·English

by  Dr. Hermann Dertinger

I
HEIDELBERG SCIENCE LIBRARY Volume 12
Hermann Dertinger . Horst Jung
Molecular
Radiation Biology
The Action of lonizing Radiation
on Elementary Biological Objects
Translated by R. P. O. Hüber and P. A. Gresham
With aPreface by K. G. Zimmer
With 116 Figures
Springer-Verlag New York . Heidelberg . Berlin 1970
Dr. H. Dertinger, Priv.-Doz. Dr. H. Jung,
Prof. Dr. K. G. Zimmer
University of Heidelberg and Institute for Radiation Blology,
Nuclear Science Center, Karlsruhe/Germany
First published in 1969 Heidelberger Taschenbücher
Band 57/58
"Molekulare Strahlenbiologie"
© by Springer-Verlag Berlin . Heidelberg 1969
ISBN-13: 978-0-387-90013-1 e-ISBN-13: 978-1-4684-6247-0
DOI: 10.1007/978-1-4684-6247-0
Thls work is subject to copyright. All rlghts are reserved, wh ether the whole or part of the
material is concerned, speclflcally those of translation, reprinting, re-use of Illustrations,
broadcasting, reproduction by photocopylng machine or similar means, and storage In data
banks.
Under § 54 of the German Copyright Law whare coples are made for other than private
use, a fee Is payable to the publlsher, the amount of the fee to be detenmined by
agreement with the publisher.
@ by Springer-Verlag Berlin • Heidelberg 1970. Library of Congress Catalog Card Number
73-112314.
The use of general descrlptive names, trade names, trade marks, etc. In thls pUblication,
even If the former are not especlally Identifled, Is not to be taken es a slgn that such
names, es understood by the Trade Marks and Merchandlse Marks Act, may accordingly
be used freely by anyone. Tltle No. 3921.
Preface
There can hardly be any doubt that radiation will continue to be an im
portant factor in our lives. Present and future advances in atomic tech
nology urgently require further work on research and development in the
field of radiation biology if the maximum benefit is to be obtained at
minimal risk from the various kinds of radiation that form a major by
product of nuclear processes. Consequently, it is also necessary to prepare
students and younger scientists for doing such work.
The present book originates from teaching experience gained in lectures,
seminars, and discussion groups started by the undersigned in 1957 and
more recently held together with Drs. Dertinger and Jung. The friendly
comments given to the German edition made us feel that it might be worth
while to put the results of our efforts at the disposal of those to whom
English is more familiar.
In agreement with the view, based on well-known facts, that most if
not aIl of the more striking practical achievements have resulted from
patient and careful investigations into some basic problem, the book aims
at introducing the reader to the methods of thought and experiment used
in molecular radiation biology as weIl as to the results obtained thereby.
This approach to the general field appears to be indicated as at the present
stage the major problems in radiation biology clearly require investigation
at the molecular, i. e. physicochemical level. Whatever practical purpose
one may have in mind (such as improvements in radiation therapy or
reducing risks by accidental exposure): careful studies of the underlying
basic mechanisms are the fastest and safest, in fact, the only way leading
to useful results.
Karlsruhe, J anuary 1970 K. G. Zimmer
v
Contents
Chapter 1. Introduction . 1
1.1. Historical Survey 2
1.2. Dose-Response Curves and Special Aspects of Radiation
Action 4
1.3. The Temporal Stages of Radiation Action. 5
1.4. The Significance of Molecular Radiation Biology 8
1.5. An Introduction to Molecular Radiation Biology 9
References . 11
Chapter 2. The Hit Theory 12
2.1. Basic Concepts . 12
2.2. Single and Multiple Hit Phenomena . 12
2.3. Dose-Response Curves of Multiple Target Systems. 14
2.4. The Influence of Biological Variability on the Form of Dose-
Response Curves 17
2.5. The "Relative Steepness" of the Dose-Response Curve . 19
2.6. Possibilities of Deception by Single-Hit Curves . 21
References . . 22
Chapter 3. The Stochastics of the Action of Radiation 24
3.1. Kinetic Interpretation of the Dose-Response Curve . 24
3.2. Multi-Hit Curves 26
3.3. Reverse Processes 28
3.4. A Formalistic Description of Dose-Response Curves 29
3.5. Dose-Response Curves of Colony Formation. 31
References . 32
VII
Chapter 4. Primary Processes of Energy Absorption 33
4.1. X- and Gamma-Radiation. 33
4.2. Neutrons. . . 37
4.3. Charged Particles 40
4.4. Uptake of Energy by Molecules 45
4.5. The Energy Distribution of Secondary Electrons . 49
4.6. Energy Deposited per Primary Interaction 52
References . . . . . . . . . . . . . 54
Chapter 5. Target Theory and Action Cross Section 55
5.1. Establishment of a Rigid Concept of a "Hit" 55
5.2. Target Theory . . . . . . . . 56
5.3. Theory of the Action Cross Section . 57
5.4. Relative Biological Effectiveness 68
References . . . . . . . . . 69
Chapter 6. Direct and Indirect Action of Radiation 70
6.1. The Direct Effect. . . . 70
6.2. Indirect Effect in Solutions . 72
6.3. Indirect Effect in Cells . . 79
6.4. Indirect Effect in the Dry State 80
6.5. Protective and Sensitizing Agents . 83
References . . . . . . . . 89
Chapter 7. The Temperature Effect . 91
7.1. Experimental Observations. 91
7.2. Temperature Effect and the Indirect Action of Radiation. 93
7.3. LET-Dependence of the Temperature Effect 97
7.4. The "Thermal Spike" Model 99
References . . . . . . 101
Chapter 8. The Oxygen Effect 102
8.1. The Oxygen Effect in Macromolecules 102
8.2. An Oxygen Effect Hypothesis . 107
VIII
8.3. The Oxygen Effect in Bacteria 110
8.4. Oxygen Effect and LET . 111
References . . . . 113
Chapter 9. The Action of Radiation on Enzymes: The Example of
Ribonuclease 115
9.1. Structure and Function of Ribonuclease 115
9.2. Inactivation Kinetics. . . 116
9.3. Radiation-Induced Radicals . 118
9.4. Changes in Irradiated Enzyme Molecules 121
9.5. Separation and Identification of Irradiation Products . 122
9.6. Amino Acid Analysis. . . 125
9.7. Mechanisms of Inactivation . 129
References . . . . . . . 132
Chapter 10. Physico-Chemical Changes in Irradiated Nucleic Acids. 134
10.1. The Structure of DNA. . 134
10.2. Radiation-Induced Radicals 136
10.3. Chemical Changes in Irradiated DNA 140
10.4. Breaks in the Polynucleotide Chains 143
10.5. Intermolecular Cross-Linking 147
10.6. Rupture of Hydrogen Bonds 150
References . . . . . . . 153
Chapter 11. Inactivation of Nucleic Acid Functions 155
11.1. Functions of Nucleic Acids 155
11.2. Infectivity . . 156
11.3. Transformation 158
11.4. Priming Activity of DNA . 163
11.5. Enzyme Induction 167
11.6. DNA-mRNA Hybrids . 168
11.7. Translation. 169
References . . . 172
IX
Chapter 12. The Action of Radiation on Viruses 174
12.1. Basic Properties of Viruses 174
12.2. Inactivation of Viruses containing Single-Stranded Nucleic
Acids 176
12.3. Inactivation of Viruses containing Double-Stranded DNA 179
12.4. Repair of Radiation Damage in Viral DNA 184
12.5. BU Effect 190
References . 193
Chapter 13. The Action of Radiation on Bacteria 195
13.1. Some Basic Properties of Bacteria 195
13.2. Inactivation of Bacteria 196
13.3. Bacterial DNA as the Critical Target. 200
13.4. Repair of UV Damage . 204
13.5. Repair of Damage caused by Ionizing Radiation 209
13.6. Genetic Control of Repair in Bacterium E. coli . 212
13.7. Micrococcus Radiodurans 215
References . 217
Chapter 14. Radiation Sensitivity and Biological Complexity 219
14.1. Attempts at a Systematic Approach 219
14.2. What is Radiation Sensitivity? 222
References 225
Subject Index 226
x
Chapter 1. Introduction
Experience has shown that an introductory survey of the field is a good
point of departure for a course of lectures. As radiation biology is an
interdisciplinary subject, a careful consideration of its meaning and scope
is, therefore, even more important than in other fields. Chemistry, for
example, is clearly defined as the science of elements and their laws of
combination and behaviour. A student of this subject acquires fairly clear
ideas of the nature of chemistry, and these require few alterations later
on. This is not the ca se with radiation biology, although at first sight it
may seem clearly defined as the science 0/ the biological action 0/ radiation.
The teaching of this subject is also different; like many other inter
disciplinary subjects, it cannot be studied for a first degree. Students
entering the field of radiation biology after the completion of theirfirst
degree find its complexity rather baffling at first; this applies even to pure
science students. A physicist, for example, having been taught in a system
atic manner, will now find that in radiation biology there are few standard
textbooks to help hirn to become farniliar with the subject.
An understanding of the problems posed by radiation biology is further
complicated by the fact that experiments in this field depend on a wide
variety of factors, even more so than in normal biological experiments.
It is therefore possible, and even understandable, that interpretations and
explanations can apparently be disproved, as the same experiment carried
out under slightly different conditions can lead to an entirely different
or even opposite set of results. This makes it difficult to recognize and
choose those experiments which are important to radiation biology. In
spite of these problems radiation biology is of special, one might almost
say "existential", interest.
The rapid development of nuclear research and technology, as well as the
wide range of applications of radiations in the treatment of disease, in
widely differing industrial production processes, for the sterilization of
drugs and medical appliances, for experiments in the food industry, and
also the use of nuclear reactors and radioactive isotopes, make it essential
to elucidate the mechanisms by which radiations act. This is the only way
in which we are likely to leam "to live successfully with ionizing ra dia
tions" (Zimmer, 1968).
1