Understanding Radiation Biology-From DNA Damage to Cancer and Radiation Risk

253 Pages·2019·25.205 MB·\253

by  Kenneth Chadwick (Author)

Understanding
Radiation Biology
From DNA Damage to Cancer
and Radiation Risk

Understanding
Radiation Biology
From DNA Damage to Cancer
and Radiation Risk
K. H. Chadwick
CRC Press
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Library of Congress Cataloging-in-Publication Data
Names: Chadwick, K. H. (Kenneth Helme), 1937- author.
Title: Understanding radiation biology : from DNA damage to cancer and radiation
risk / by Kenneth Chadwick.
Description: Boca Raton: CRC Press, [2020] | Includes bibliographical references and index.
Identifiers: LCCN 2019031202 (print) | LCCN 2019031203 (ebook) | ISBN 9780367253769
(paperback) | ISBN 9780367255152 (hardback) | ISBN 9780429288197 (ebook)
Subjects: LCSH: Radiobiology.
Classification: LCC QH543.5 .C44 2020 (print) | LCC QH543.5 (ebook) | DDC 571.4/5--dc23
LC record available at https://lccn.loc.gov/2019031202
LC ebook record available at https://lccn.loc.gov/2019031203
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Contents Contents
To my wife, Hilary, my daughters, Carolyn and Victoria,
and my Bichon Frisé, Bonnie

Contents
Prologue ....................................................................................................................xi
Acknowledgements ..................................................................................................xv
PART I Ionising Radiation Effects
Chapter 1 The Molecular Model and DNA Double Strand Breaks ......................3
1.1 The Molecular Model Hypothesis –
The Basic Concepts ...................................................................3
1.2 The Induction of DNA Double Strand Breaks ..........................4
1.3 The Linear–Quadratic Function and DNA Double Strand
Breaks ........................................................................................5
1.4 The Alpha Mode of Double Strand Break Induction ................6
1.5 The Beta Mode of Double Strand Break Induction ...................8
1.6 The Influence of Repair ...........................................................10
1.6.1 Single Strand Break Repair ........................................10
1.6.2 Double Strand Break Repair ......................................11
1.7 The Experimental Evidence for the Linear–Quadratic
Dose Response of Radiation-Induced DNA Double
Strand Breaks ..........................................................................12
1.8 Inferences, Implications and Insights ......................................16
1.8.1 The Alpha Mode of Radiation Action ........................18
1.8.2 The Beta Mode of Radiation Action ..........................19
1.9 Conclusions ..............................................................................20
Chapter 2 The Molecular Model for Cellular Effects .........................................21
2.1 The Relationship of Double Strand Breaks to Cellular
Effects ......................................................................................21
2.2 Cell Survival ............................................................................21
2.3 Chromosomal Aberrations ......................................................23
2.4 Mutation Frequency .................................................................24
2.5 The Linear–Quadratic Equation and Data Analysis ...............26
2.5.1 Survival of Synchronous Cells ...................................26
2.5.2 The Influence of Different Exposure Conditions
on the Linear and Quadratic Coefficients ..................31
2.6 The Micro-Dosimetry Problem ...............................................34
2.7 Conclusions ..............................................................................38
vii
viii Contents
Chapter 3 The Link from Molecular Lesion to Cellular Effects ........................41
3.1 The Correlations between DNA Double Strand Breaks
and Cellular Effects .................................................................41
3.2 The Correlation between DNA Double Strand Breaks
and Cell Survival .....................................................................42
3.3 The Correlation between Chromosomal Aberration Yield
and Cell Survival .....................................................................51
3.4 The Correlation between Mutation Frequency and
Cell Survival ............................................................................54
3.5 An Implied Correlation ...........................................................61
3.6 Conclusions ..............................................................................63
Chapter 4 DNA Double Strand Breaks and Chromosomal Aberrations ............65
4.1 Introduction .............................................................................65
4.2 Recombination Repair of DNA Double Strand
Breaks ......................................................................................66
4.3 Repair of DNA Double Strand Breaks and the
Formation of Chromosomal Aberrations ................................68
4.4 Strong Supporting Evidence ....................................................76
4.5 Complex Rearrangements .......................................................78
4.6 Additional Comments ..............................................................79
4.6.1 Other Aberration Formation Theories .......................79
4.6.2 Repetitive DNA ..........................................................79
4.6.3 Non-Homologous End Joining and Micro-
Homology-Enabled Recombination Repair................80
4.7 Telomere to Break Rejoining ..................................................81
4.8 Mutations .................................................................................82
4.9 Conclusions ..............................................................................83
Chapter 5 The Effect of Dose Rate, Fractionation and Post-Irradiation Repair ......85
5.1 Introduction .............................................................................85
5.2 The Repair of DNA Single Strand Breaks and the Dose
Rate Effect ...............................................................................85
5.2.1 Three Exposure Time Regions ...................................87
5.3 Experimental Measurements of the Dose Rate Effect ............90
5.3.1 Cell Survival ...............................................................91
5.3.2 Chromosome Aberrations ..........................................93
5.3.3 Mutation Frequency ...................................................94
5.4 The Effect of Dose Fractionation ............................................97
5.4.1 The Influence of Post-Irradiation Repair .................102
5.4.2 The Repair of DNA Single Strand Breaks
between Fractions .....................................................102
5.4.3 Further Analytical Possibilities ................................103
5.4.4 Other Published Data ...............................................104
Contents ix
5.5 The Effect of Post-Irradiation Repair ....................................107
5.5.1 Cell Survival .............................................................107
5.5.2 Chromosome Aberrations ........................................108
5.5.3 Mutation Frequency .................................................109
5.6 Conclusions ............................................................................111
Chapter 6 Radiation Quality .............................................................................113
6.1 Introduction ...........................................................................113
6.2 Relative Biological Effectiveness ..........................................115
6.3 A Qualitative Appreciation of the Effect of Radiation
Quality ...................................................................................117
6.4 A Quantitative Appreciation of the Effect of Radiation
Quality ...................................................................................121
6.5 The Biological Effectiveness of Sparsely
Ionising Radiations ................................................................130
6.6 Conclusions ............................................................................132
Chapter 7 Radiation-Induced Cancer ................................................................133
7.1 Stochastic Effect ....................................................................133
7.2 Experimental Data .................................................................136
7.3 Dose Rate...............................................................................140
7.4 Human Data ...........................................................................142
7.5 Cancer in Children and Young Adults ..................................146
7.5.1 Childhood Cancers ...................................................147
7.5.2 Cancer in Young Adults ...........................................148
7.6 Conclusions ............................................................................149
Chapter 8 Radiation-Induced Lethality ............................................................151
8.1 Radiation-Induced Lethality..................................................151
8.2 The Effect of Dose Rate ........................................................154
8.3 The Effect of Radiation Quality ............................................157
8.4 Conclusions ............................................................................159
Chapter 9 Radiological Protection ....................................................................161
9.1 Introduction ...........................................................................161
9.2 Linear No-Threshold Concept ...............................................161
9.3 The Dose and Dose Rate Effectiveness Factor ......................164
9.4 The Weighting Factor of Sparsely Ionising Radiation and
Dose Equivalent .....................................................................165
9.5 A Potential Way Forward ......................................................167
9.6 Insights into Radiological Protection Risk from Cancer
Modelling ..............................................................................168