Biomolecular Action of Ionizing Radiation: 1st Edition (Paperback) book cover

Biomolecular Action of Ionizing Radiation

1st Edition

By Shirley Lehnert

CRC Press

560 pages | 4 Color Illus. | 174 B/W Illus.

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Paperback: 9780750308243
pub: 2007-10-24
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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.

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

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

About the Originator

About the Series

Series in Medical Physics and Biomedical Engineering

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
SCI055000
SCIENCE / Physics