Biomolecular Action of Ionizing Radiation Book

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