1st Edition

Biomolecular Action of Ionizing Radiation




ISBN 9780750308243
Published October 24, 2007 by CRC Press
560 Pages 4 Color & 174 B/W Illustrations

USD $120.00

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Book Description

Embracing the transformation of radiation sciences by the recent surge of developments in molecular biology, this progressive text offers an up-to-date analysis of in vitro and in vivo molecular responses in the body induced by ionizing radiation. With a unique emphasis on medical physics applications, Biomolecular Action of Ionizing Radiation also presents a much needed, in-depth perspective on clinical applications for the treatment of cancer and radiation injuries.

Based on a popular course given by the author at McGill University,the bookplaces the traditional tenets of radiation biology in the context of contemporary cell and molecular biology. Using terms that non-experts in molecular biology can understand, it clarifies the underlying mechanisms of radiation effects on molecular interactions including signal transduction pathways, modes of cell killing, and non-targeted effects. The author subsequently associates key principles and advances with potential applications, including the use of ionizing radiation as a cytotoxic and cytostatic agent, and radiosensitization by targeting molecular intermediates or signaling molecules involved in radiation-induced processes.

Raising the standard for radiation biology texts that are currently available, Biomolecular Action of Ionizing Radiation is an outstanding resource for advanced undergraduate and graduate students in medical physics, radiation oncology, radiation biology, and those who have an interest in the radiation sciences and in cancer treatment.

Table of Contents

INTRODUCTION
BASIC RADIATION PHYSICS AND CHEMISTRY
Ionization and Excitation
Types of Ionizing Radiation
Electromagnetic Radiation
Particulate Radiations
Processes of Energy Absorption
Direct and Indirect Action of Radiation
Radiolysis of Water
Haber–Weiss Reaction
Reactions of the Primary Radiolytic Products of Water with Target Molecules
Solute Radicals Form Stable Products
Linear Energy Transfer
Relative Biological Effectiveness
BASIC CELL BIOLOGY AND MOLECULAR GENETICS
Basic Cell Biology
Cell Membrane
Cytoplasm
Nucleus
Mitochondria
Endoplasmic Reticulum and Ribosomes
Golgi Complex
Cytoskeleton
Lysosomes
Extracellular Materials
Molecular Genetics
DNA Structure
DNA Structure Is the Basis for Heredity
Mechanism of DNA Replication
Transcribing DNA to RNA
From RNA to Protein
Proteins
METHODS OF CELL AND MOLECULAR RADIOBIOLOGY
Methods of Classical Radiobiology
Cell Survival In Vitro: The Clonogenic Assay
Non-Clonogenic Assays
Methods of Cell Synchronization
Determination of Duration of Phases of the Cell Cycle
Measuring Cell Survival In Vivo
Methods for Detecting Damage to DNA
Strand Break Assays
Measurement of DNA Damage and Repair in Individual Mammalian Cells
Tools and Techniques of Molecular Biology
Hybridization of Nucleic Acids
Restriction Enzymes
Gel Electrophoresis and Blotting Techniques
Polymerase Chain Reaction
Putting New Genes into Cells: DNA-Mediated Gene Transfer
Generation of a Cloned Probe or DNA Library
Sequencing of DNA
Single Nucleotide Polymorphisms
Functional Inactivation of Genes
Genomic Methods of Tumor Analysis
Analysis of Proteins
Production of Monoclonal Antibodies
Proteomics: Analysis of Protein Structure and Function
Analysis of Tissue Sections and Single Cells
Laser Capture Microdissection
IONIZING RADIATION EFFECTS TO THE CYTOPLASM
Oxidative Stress
Metabolic Oxidative Stress
Ionizing Radiation-Induced ROS/RNS
Demonstration of Radiation-Induced Intracellular ROS/RNS
Mechanisms of Generation and Amplification of ROS/RNS Following Irradiation of the Cytoplasm
Consequences of Radiation-Induced Generation of ROS/RNS
Effects of Ionizing Radiation on the Cell Membrane
Structure of the Cell Membrane
Lipid Peroxidation in Plasma Membranes
Consequences of Damage to Plasma Membrane Lipids
Plasma Membrane Is a Target for Ionizing Radiation-Induced Apoptosis
DAMAGE TO DNA BY IONIZING RADIATION
Mechanisms of DNA Damage: Physicochemical Relationships
Mechanisms of Damage Induction: Chemical End Points
Mechanisms of Damage Induction: Cellular End Points
Types of DNA Damage
Simple Damages to DNA: Base Damage and Single-Strand Breaks
Apurinic or Apyrimidinic Sites
Modifiers of Radiation Effect
DNA Strand Breaks
Double-Strand Breaks and Other Multiply Damaged Sites
Distribution of MDS
Clustered Damage in DNA of Mammalian Cells
DNA-Protein Cross-Links
REPAIR OF RADIATION DAMAGE TO DNA
Overview of DNA Repair Mechanisms
Repair of Radiation-Induced DNA Damage
Repair of Base Damage and Single-Strand DNA Breaks: Base Excision Repair
Role of PARP
Processing of Multiply Damaged Sites by BER
Repair of DNA Double-Strand Breaks
Homologous Recombination
Nonhomologous End Joining
Genes and Proteins Involved in NHEJ
Telomere-Bound Proteins and DNA Repair
Human Syndromes Involving DNA Repair Deficiency
Relationship between DNA Repair and Cell Survival
CELLULAR RESPONSE TO DNA DAMAGE
Passing on the Message that DNA Has Been Damaged
Signal Transduction
Signal Transduction Cascade Initiated by Radiation-Induced DNA Damage
ATM Protein
Functions of ATM
How Does ATM Respond to Radiation-Induced DNA Damage?
Role of ATM in DNA Repair
ATM and the MRN Complex
Tumor Suppressor Gene p53
Turnover of p53: Mdm2
Modulation of p53 Stability and Activity
Radiation-Induced Growth Arrest
Cell Cycle: Cyclins and Cyclin Dependent Kinases.
Radiation-Induced Cell-Cycle Arrest
Oncogenes and Cell-Cycle Checkpoints
Variation in Radiosensitivity through the Cell Cycle
P53-Mediated Apoptosis
CHROMATIN STRUCTURE AND RADIATION SENSITIVITY
Cell Nucleus
Hierarchical Structure of Chromatin
Structure and Function: Chromatin and the Nuclear Matrix
Protection of DNA from Radiation Damage by Nuclear Proteins
DNA-Protein Cross-Link Formation
DSB Yields and RBE
Role of Polyamines
Radiation Sensitivity and the Stability of the DNA–Nuclear Matrix
Radiosensitivity of Condensed Chromatin
Role of Chromatin in DNA DSB Recognition and Repair
Histone 2AX
ATM Signaling from Chromatin
Modulation of Chromatin Structure and Function by Acetylation
Radiosensitization by Histone Deacetylase Inhibitors
RADIATION-INDUCED CHROMOSOME DAMAGE
DNA, Chromosomes, and the Cell Cycle
Organization of DNA into Chromatin and Chromosomes
Cell Cycle
Mitosis
Radiation-Induced Chromosome Aberrations
Nature of the Initial Lesion
Partial Catalog of Chromosome and Chromatid Aberrations
Visualization of Chromosome Breaks during Interphase: Premature Chromosome Condensation
FISH, mFISH, SKY, mBAND FISH, and Chromosome Painting
Results of Whole Chromosome Painting
Mechanisms of Aberration Formation
Chromosome Localization and Proximity Effects
Implications of Chromosome Damage
Genetics
Carcinogenesis
Cell Survival, Dose Rate, and Fractionation Response
Genomic Instability
Biodosimetry and Risk Estimation
MODULATION OF RADIATION RESPONSE VIA SIGNAL TRANSDUCTION PATHWAYS
Intracellular Signaling
Transmembrane Receptors
ErbB Family of Receptor Kinases
Cytoplasmic Signaling
Ras Proto-Oncogene Family
Signal Transduction Cascades
Modulation of Radiation Response by Interaction of Signal Transduction Pathways
Activation of ErbB Receptors by Ionizing Radiation
Mechanism of Receptor Activation by Ionizing Radiation
Role of Other Growth Factors
Effects of Activation of GF Receptors on Cell Survival
Autocrine Signaling
Radiosensitization by Modulation of Signal Transduction Intermediates: Molecular Radiosensitizers
ErbB Family Signal Inhibitors
Clinical Applications of EGFR Signal Inhibitors
Inhibition of the Ras-Mediated Signaling Pathway
Clinical Application of Farnesyl Transferase Inhibitors
Clinical Implications of Radiation-Induced Cell Signaling: Accelerated Cell Proliferation
RADIATION-INDUCED APOPTOSIS
Apoptosis
Mechanisms of Apoptosis
Caspases
Apoptotic Signaling Pathways
Intrinsic Apoptotic Signaling: The Mitochondrial Pathway
Extrinsic Apoptotic Signaling
Extrinsic Apoptotic Signaling Initiated at the Plasma Membrane: The Ceramide Pathway
Why Do Some Cells Die as the Result of Apoptosis and Not Others?
Apoptotic Processes and the In Vivo Radiation Response
Normal Tissue
Tumor Response
EARLY AND LATE RESPONDING GENES INDUCED BY IONIZING RADIATION
Gene Expression Is Induced by Ionizing Radiation
Transcription Factors
Important Transcription Factors Activated by Radiation
Radiation-Gene Therapy
Early and Late Response Genes
Induction of Late Response Genes by Ionizing Radiation
Cytokine-Mediated Responses in Irradiated Tissues
Late Effects: Radiation-Mediated Fibrosis
Gene Expression Associated with Radiation-Mediated Vascular Damage
Cytokines as Therapeutic Agents: Radioprotection and Radiosensitization
Radiosensitization
Radioprotection
Cytokines as Biomarkers of Radiation Exposure
CELL DEATH, CELL SURVIVAL, AND ADAPTATION
Cell Death
Modes of Cell Death in Nonirradiated Cells
Radiation-Induced Cell Death
Role of p53
Quantitating Cell Kill: Analysis of Cell Survival Curves
Target Theory
Linear Quadratic Model
Lethal, Potentially Lethal Damage Model
Repair Saturation Models
Cell Survival at Low Radiation Doses
Low Dose Hypersensitivity
Adaptive Response
Interactions of Adaptive Response and Bystander Effects
Implications of Low Dose Effects for Risk Assessment
Exposure to Background Radiation
Adaptive Response and Neoplastic Transformation
Clinical Implications of Low Dose Effects
BYSTANDER EFFECTS AND GENOMIC INSTABILITY
Dogma of Radiation Biology
Bystander Effects
Bystander Effects In Vitro
Bystander Effects Seen after Transfer of Medium from Irradiated Cells
Bystander Effects In Vivo
Mechanisms Underlying Radiation-Induced Bystander Effects
Implications in Risk Assessment
Genomic Instability
Genomic Instability In Vitro: Delayed Responses to Radiation Exposure
Demonstration of Genomic Instability In Vivo
Genomic Instability and Cancer
Mechanisms Underlying Radiation-Induced Genomic Instability
Relationship between Radiation-Induced Bystander Effects and Genomic Instability
TUMOR RADIOBIOLOGY
Tumor Radiobiology
Unique Tumor Microenvironment
Interstitial Fluid Pressure
Tumor Hypoxia
Tumor Acidosis
Tumor Metabolism: Aerobic and Anaerobic Glycolysis
Tumor Microenvironment Creates Barriers to Conventional Therapies
Chemotherapy
Radiotherapy
Measurement of Tumor Hypoxia
Radio-Sensitization by Modifying Tumor Oxygenation
Effect of Hypoxia on Tumor Development and Progression
Targeting the Ubiquitin/Proteasome System
RADIATION BIOLOGY OF NONMAMMALIAN SPECIES: THREE EUKARYOTES AND A BACTERIUM
Introduction: Lower Eukaryotes in Radiation Research
Yeast, a Single-Celled Eukaryote
Radiation Biology of Yeast
Radiosensitive Mutants for the Study of DNA Repair
DNA Damage Checkpoints
Genome Wide-Screening for Radiation Response-Associated in Yeast
Caenorhabditis elegans
Apoptosis in C. elegans
Cell Cycle Checkpoints in C. elegans
DNA Repair in Celegans
DNA Damage Responses in C. elegans
Radiation-Induced Mutation
Worms in Space
Zebrafish
Zebrafish for the Evaluation of Genotoxic Stress
Effects of Ionizing Radiation on Brain and Eye Development
Modulation of Radiation Response
Gene Function during Embryonic Development
Hematological Studies with Zebra Fish
Deinococcus radiodurans
Origins of Extremophiles
Genetics of D. radiodurans
Characteristics of D. radiodurans Predisposing to Radiation Resistance
Regulation of Cellular Responses to Extensive Radiation Damage
Double-Strand Break Tolerance
An Economic Niche for D. radiodurans
References
Glossary
Index
* Each Chapter contains a Summary section and References

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Author - Shirley  Lehnert
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Shirley Lehnert

Professor, McGill University
Montreal, Quebec, Canada

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Reviews

"… The new textbook is targeted at students in radiation oncology and medical physics and should be a useful resource for graduate students with interests in radiation sciences and cancer treatment. … Overall, I felt the author has generally achieved the aim of developing a textbook on applications of molecular biology to radiation biology relating to radiation oncology. …"
Crystallography Reviews, Vol. 15, No. 2, April-June 2009

"The major strength of this book likes in its in-depth coverage of recent advances in radiation-induced signal transduction pathways and molecular mechanisms of cellular responses to ionizing radiation . . . succeeded in providing an up-to-date synopsis of the field of radiation research in the early 21st century and is a worthy addition to the library of didactic textbooks in our field. This book has a comprehensive and clearly laid out table of contents. The text is succinct and easy to read. This book certainly belongs on the bookshelf of anyone who is interested in understanding radiation biology including residents, graduate students, and postdoctoral researchers. In particular, radiation oncology residents will find this book to be an excellent source of information for understanding the molecular basis of radiation biology."

– Zhong Yun and Joann B. Sweasy, Department of Therapeutic Radiology, Yale University School of Medicine, 2009

". . . this progressive text offers an up-to-date analysis of in vitro and in vivo molecular responses in the body induced by ionizing radiation. With a unique emphasis on medical physics applications, this volume also presents a much needed, in-depth perspective on clinical applications for the treatment of cancer and radiation injuries . . . an outstanding resource for advanced undergraduate and graduate students in medical physics, radiation oncology, radiation biology, and those who have an interest in the radiation sciences and in cancer treatment."

–In Anticancer Research, Nov-Dec 2008, Vol. 28, No. 6B