Effects of Ionizing Radiation on DNA
Springer-Verlag Berlin and Heidelberg GmbH & Co. K
978-3-540-08542-3 (ISBN)
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If, as is probable, the energy is to be mainly of nuclear origin, we must expect a marked ex- pansion of the nuclear industry, which could well become the world's leading industry in the not-too-distant future. This would carry with it the problems caused by the presence of enor- mous quantities of radioactivity, despite the stringent precau- tions taken to date and those to be taken in future.
Section I: Physical Aspects.- 1 Structure and Electronic Properties of DNA.- 1.1 Nomenclature and Primary Structure of DNA.- 1.2 Dimensions and Conformations.- 1.2.1 The Bases.- 1.2.2 The Nucleosides and Nucleotides.- 1.2.3 DNA.- 1.3 Electronic Properties.- 1.3.1 Molecular Orbital Calculations.- 1.3.2 Absorption Spectra.- 1.4 Interactions.- 1.4.1 In-Plane Interactions: The Hydrogen Bonds.- 1.4.2 Vertical Associations: The Stacking of the Bases.- 1.4.3 The Role of the Sugar-Phosphate Backbone.- 1.4.4 The Stability of the DNA Helix.- 1.4.5 Interactions with Aromatic Molecules.- 2 Interaction of Ionizing Radiation with Matter.- 2.1 Introduction.- 2.2 Ionizing Radiation.- 2.3 Degradation Spectra and Linear Energy Transfer (LET).- 2.4 Primary Processes and Primary Products.- 2.5 Activation Spectra.- 2.6 Superexcited States.- 2.7 Inner-Shell Ionizations.- 2.8 Slow Particles.- 2.9 Direct and Indirect Effects. Energy Transfer.- 2.10 Radiation Yield. G-Value.- 3 Structure of Radicals from Nucleic Acid Constituents.- 3.1 Introduction.- 3.2 Base Radicals.- 3.2.1 Hydrogen Addition to Purines.- 3.2.2 Hydrogen Addition to Pyrimidines.- 3.2.2.1 5-yl Radicals.- 3.2.2.2 6-yl Radicals.- 3.2.2.3 >?-OH Radicals.- 3.2.3 Hydrogen-Abstraction Radicals.- 3.2.3.1 Abstraction from Pyrimidine Rings.- 3.2.3.2 Abstraction from Substituent Groups to Pyrimidines and Purines.- 3.2.4 Molecular Ion Radicals.- 3.3 Sugar-Phosphate Backbone Radicals.- 3.4 Molecular Orbital Calculations.- 3.5 Radical Formation Mechanisms.- 4 Structure of Radicals from Nucleic Acids.- 4.1 Frozen Solution and Dry State.- 4.1.1 Radiolysis of DNA in Frozen Solution.- 4.1.2 Radicals from Solid Nucleic Acids.- 4.2 Oriented Fibers.- 4.2.1 The Wet Spinning Method.- 4.2.2 ESR Results.- 5 Radical Yields.- 5.1 General Aspects.- 5.2 Yields in Constituents.- 5.2.1 Solid Bases, Nucleosides and Nucleotides.- 5.2.2 Influence of Environmental, Parameters.- 5.2.2.1 Temperature.- 5.2.2.2 Crystallinity.- 5.2.2.3 Glasses.- 5.3 Yields in Nucleic Acids.- 5.3.1 Influence of Environmental Parameters.- 5.3.1.1 Effect of Moisture Content.- 5.3.1.2 Effect of Molecular Weight.- 5.3.1.3 Yields at Room Temperature.- 5.3.1.4 Effect of Temperature.- 5.3.1.5 Glasses 9.- 5.3.2 Comparison with Yields in Constituents.- 6 Radiomimetic Radical Production.- 6.1 Introduction.- 6.2 Interaction with H-Atoms and OH-Radicals.- 6.2.1 Addition and Abstraction Reactions with Nucleic Acid Bases and Sugars.- 6.2.2 Reactions with Nucleic Acids.- 6.3 Reaction with Electrons.- 6.3.1 ESR Characteristics of the Pyrimidine and Purine Anion Radicals.- 6.3.1.1 Pyrimidine Derivatives.- 6.3.1.2 Purine Derivatives.- 6.3.2 Conversion of the Anion Radicals.- 6.3.2.1 Pyrimidine Base Anions as Precursors of H-Addition Radicals.- 6.3.2.2 Dehalogenation Radicals in 5-Halouracils.- 6.3.2.3 Protonation Reactions of Purine Anions.- 6.4 Interaction with Excited Inert Gases.- 6.4.1 Purine and Pyrimidine Derivatives.- 6.4.2 DNA.- 6.4.3 Mechanisms of Radical Formation.- 7 Transfer Phenomena.- 7.1 Introduction.- 7.2 Substituent Effects.- 7.2.1 Barbituric Acid and Derivatives.- 7.2.2 5-Halogen-Substituted Uracil Bases and Nucleosides.- 7.3 Electron Transfer in ?-Irradiated DNA.- 7.3.1 Preliminary ESR Experiments on ?-Irradiated DNA.- 7.3.2 Mechanical Mixtures and Molecular Complexes of DNA Nucleotides.- 7.3.3 A Working Hypothesis for Internucleo-tide Spin-Transfer Processes.- 7.3.4 Other Examples of Intermolecular Spin-Transfer Processes.- 7.3.5 Formal Analysis of ESR Spectra of Dry DNA.- 7.4 Photosensitization by Dyes in Frozen Solutions.- 7.4.1 Nature of the Photosensitizers.- 7.4.2 Free Radicals Induced in Nucleotides.- 7.4.2.1 Description and Interpretation of the ESR Spectra.- 7.4.2.2 Mechanism of Radical Formation.- 7.4.2.3 Influence of Oxygen.- 7.4.2.4 Influence of the Relative Molar Concentration of Dye and Substrate.- 7.4.2.5 Influence of Dye Aggregation.- 7.4.3 Free Radicals Induced in DNA.- 7.4.3.1 Description and Interpretation of the ESR Spectra.- 7.4.3.2 Mechanism of Formation: Anionic Stage.- 7.4.3.3 Quantitative Influence of Oxygejn and Ionic Strength.- 7.4.4 General Conclusions.- References.- Section II: Chemical Aspects.- 1 Primary Events in the Radiolysis of Aqueous Solutions of Nucleic Acids and Related Substances.- 1.1 Reactive Species in Irradiated Aqueous Systems.- 1.2 Rates of Reaction with the Primary Species.- 1.3 Intermediates in the Radiolysis of Aqueous Solutions of Nucleic Acids and Their Components.- 1.3.1 Reaction with Hydroxyl Radicals.- 1.3.1.1 Pyrimidines.- 1.3.1.2 Purines.- 1.3.1.3 Nucleosides, Nucleotides and Polynucleotides.- 1.3.2 Reaction with Hydrogen Atoms.- 1.3.3 Reaction with the Solvated Electron.- 1.3.4 Reactions of the Intermediates with Added Solutes.- 1.3.4.1 Oxygen.- 1.3.4.2 Electron-Transfer Processes.- 2 Radiation-Induced Degradation of the Base Component in DNA and Related Substances - Final Products.- 2.1 Introduction.- 2.2 Nucleic Acid Constituents in Aqueous Aerated Solutions.- 2.2.1 Free Bases.- 2.2.1.1 Thymine.- 2.2.1.2 Uracil.- 2.2.1.3 Cytosine.- 2.2.1.4 5-Bromouracil.- 2.2.1.5 Adenine.- 2.2.2 Nucleosides and Nucleotides.- 2.2.2.1 Thymidine.- 2.2.2.2 5-Bromo-2?-Deoxyuridine.- 2.2.2.3 Uridine.- 2.2.2.4 Deoxyadenosine.- 2.2.2.5 Nucleotides - Thymidylic Acid and Uridylic Acid.- 2.2.2.6 Dinucleotides - TpT.- 2.3 Nucleic Acid Constituents in Deaerated Aqueous Solutions.- 2.3.1 Free Bases.- 2.3.1.1 Thymine.- 2.3.1.2 Uracil.- 2.3.1.3 Cytosine.- 2.3.1.4 Adenine.- 2.3.2 Free Bases in the Presence of a Second Solute.- 2.3.2.1 Bases and Ethanol.- 2.3.2.2 Thymine and Radiosensitizers.- 2.3.2.3 Pyrimidine Bases and Surfactants.- 2.3.2.4 Pyrimidine Bases and Amino Acids.- 2.3.3 Nucleosides and Nucleotides.- 2.3.3.1 Thymidine.- 2.3.3.2 Purine Nucleosides and Nucleotides.- 2.4 Nucleic Acid Constituents in Solid State or in Frozen Solutions.- 2.5 DNA in Aerated and Deaerated Solutions.- 2.5.1 Modifications of the Base Moieties in the Polynucleotide Chain.- 2.5.1.1 UV Absorption and IR Spectra.- 2.5.1.2 Formic or Perchloric Acid Hydrolysis - Base Destruction.- 2.5.1.3 Peroxidation of Pyrimidines.- 2.5.1.4 Indirect Determinations of the Fairly Stable Products.- 2.5.1.5 Direct Determinations of the Fairly Stable Products.- 2.5.2 Products Released from the Polynucleotide Chain.- 2.5.2.1 3H-H2O from DNA Thymine Methyl-(3H).- 2.5.2.2 Ammonia.- 2.5.2.3 Free Bases.- 2.5.2.4 Products of Base Component Degradation -?-OH Radicals.- 3.2.3 Hydrogen-Abstraction Radicals.- 3.2.3.1 Abstraction from Pyrimidine Rings.- 3.2.3.2 Abstraction from Substituent Groups to Pyrimidines and Purines.- 3.2.4 Molecular Ion Radicals.- 3.3 Sugar-Phosphate Backbone Radicals.- 3.4 Molecular Orbital Calculations.- 3.5 Radical Formation Mechanisms.- 4 Structure of Radicals from Nucleic Acids.- 4.1 Frozen Solution and Dry State.- 4.1.1 Radiolysis of DNA in Frozen Solution.- 4.1.2 Radicals from Solid Nucleic Acids.- 4.2 Oriented Fibers.- 4.2.1 The Wet Spinning Method.- 4.2.2 ESR Results.- 5 Radical Yields.- 5.1 General Aspects.- 5.2 Yields in Constituents.- 5.2.1 Solid Bases, Nucleosides and Nucleotides.- 5.2.2 Influence of Environmental, Parameters.- 5.2.2.1 Temperature.- 5.2.2.2 Crystallinity.- 5.2.2.3 Glasses.- 5.3 Yields in Nucleic Acids.- 5.3.1 Influence of Environmental Parameters.- 5.3.1.1 Effect of Moisture Content.- 5.3.1.2 Effect of Molecular Weight.- 5.3.1.3 Yields at Room Temperature.- 5.3.1.4 Effect of Temperature.- 5.3.1.5 Glasses 9.- 5.3.2 Comparison with Yields in Constituents.- 6 Radiomimetic Radical Production.- 6.1 Introduction.- 6.2 Interaction with H-Atoms and OH-Radicals.- 6.2.1 Addition and Abstraction Reactions with Nucleic Acid Bases and Sugars.- 6.2.2 Reactions with Nucleic Acids.- 6.3 Reaction with Electrons.- 6.3.1 ESR Characteristics of the Pyrimidine and Purine Anion Radicals.- 6.3.1.1 Pyrimidine Derivatives.- 6.3.1.2 Purine Derivatives.- 6.3.2 Conversion of the Anion Radicals.- 6.3.2.1 Pyrimidine Base Anions as Precursors of H-Addition Radicals.- 6.3.2.2 Dehalogenation Radicals in 5-Halouracils.- 6.3.2.3 Protonation Reactions of Purine Anions.- 6.4 Interaction with Excited Inert Gases.- 6.4.1 Purine and Pyrimidine Derivatives.- 6.4.2 DNA.- 6.4.3 Mechanisms of Radical Formation.- 7 Transfer Phenomena.- 7.1 Introduction.- 7.2 Substituent Effects.- 7.2.1 Barbituric Acid and Derivatives.- 7.2.2 5-Halogen-Substituted Uracil Bases and Nucleosides.- 7.3 Electron Transfer in ?-Irradiated DNA.- 7.3.1 Preliminary ESR Experiments on ?-Irradiated DNA.- 7.3.2 Mechanical Mixtures and Molecular Complexes of DNA Nucleotides.- 7.3.3 A Working Hypothesis for Internucleo-tide Spin-Transfer Processes.- 7.3.4 Other Examples of Intermolecular Spin-Transfer Processes.- 7.3.5 Formal Analysis of ESR Spectra of Dry DNA.- 7.4 Photosensitization by Dyes in Frozen Solutions.- 7.4.1 Nature of the Photosensitizers.- 7.4.2 Free Radicals Induced in Nucleotides.- 7.4.2.1 Description and Interpretation of the ESR Spectra.- 7.4.2.2 Mechanism of Radical Formation.- 7.4.2.3 Influence of Oxygen.- 7.4.2.4 Influence of the Relative Molar Concentration of Dye and Substrate.- 7.4.2.5 Influence of Dye Aggregation.- 7.4.3 Free Radicals Induced in DNA.- 7.4.3.1 Description and Interpretation of the ESR Spectra.- 7.4.3.2 Mechanism of Formation: Anionic Stage.- 7.4.3.3 Quantitative Influence of Oxygejn and Ionic Strength.- 7.4.4 General Conclusions.- References.- Section II: Chemical Aspects.- 1 Primary Events in the Radiolysis of Aqueous Solutions of Nucleic Acids and Related Substances.- 1.1 Reactive Species in Irradiated Aqueous Systems.- 1.2 Rates of Reaction with the Primary Species.- 1.3 Intermediates in the Radiolysis of Aqueous Solutions of Nucleic Acids and Their Components.- 1.3.1 Reaction with Hydroxyl Radicals.- 1.3.1.1 Pyrimidines.- 1.3.1.2 Purines.- 1.3.1.3 Nucleosides, Nucleotides and Polynucleotides.- 1.3.2 Reaction with Hydrogen Atoms.- 1.3.3 Reaction with the Solvated Electron.- 1.3.4 Reactions of the Intermediates with Added Solutes.- 1.3.4.1 Oxygen.- 1.3.4.2 Electron-Transfer Processes.- 2 Radiation-Induced Degradation of the Base Component in DNA and Related Substances - Final Products.- 2.1 Introduction.- 2.2 Nucleic Acid Constituents in Aqueous Aerated Solutions.- 2.2.1 Free Bases.- 2.2.1.1 Thymine.- 2.2.1.2 Uracil.- 2.2.1.3 Cytosine.- 2.2.1.4 5-Bromouracil.- 2.2.1.5 Adenine.- 2.2.2 Nucleosides and Nucleotides.- 2.2.2.1 Thymidine.- 2.2.2.2 5-Bromo-2?-Deoxyuridine.- 2.2.2.3 Uridine.- 2.2.2.4 Deoxyadenosine.- 2.2.2.5 Nucleotides - Thymidylic Acid and Uridylic Acid.- 2.2.2.6 Dinucleotides - TpT.- 2.3 Nucleic Acid Constituents in Deaerated Aqueous Solutions.- 2.3.1 Free Bases.- 2.3.1.1 Thymine.- 2.3.1.2 Uracil.- 2.3.1.3 Cytosine.- 2.3.1.4 Adenine.- 2.3.2 Free Bases in the Presence of a Second Solute.- 2.3.2.1 Bases and Ethanol.- 2.3.2.2 Thymine and Radiosensitizers.- 2.3.2.3 Pyrimidine Bases and Surfactants.- 2.3.2.4 Pyrimidine Bases and Amino Acids.- 2.3.3 Nucleosides and Nucleotides.- 2.3.3.1 Thymidine.- 2.3.3.2 Purine Nucleosides and Nucleotides.- 2.4 Nucleic Acid Constituents in Solid State or in Frozen Solutions.- 2.5 DNA in Aerated and Deaerated Solutions.- 2.5.1 Modifications of the Base Moieties in the Polynucleotide Chain.- 2.5.1.1 UV Absorption and IR Spectra.- 2.5.1.2 Formic or Perchloric Acid Hydrolysis - Base Destruction.- 2.5.1.3 Peroxidation of Pyrimidines.- 2.5.1.4 Indirect Determinations of the Fairly Stable Products.- 2.5.1.5 Direct Determinations of the Fairly Stable Products.- 2.5.2 Products Released from the Polynucleotide Chain.- 2.5.2.1 3H-H2O from DNA Thymine Methyl-(3H).- 2.5.2.2 Ammonia.- 2.5.2.3 Free Bases.- 2.5.2.4 Products of Base Component Degradation -?-OH Radicals.- 3.2.3 Hydrogen-Abstraction Radicals.- 3.2.3.1 Abstraction from Pyrimidine Rings.- 3.2.3.2 Abstraction from Substituent Groups to Pyrimidines and Purines.- 3.2.4 Molecular Ion Radicals.- 3.3 Sugar-Phosphate Backbone Radicals.- 3.4 Molecular Orbital Calculations.- 3.5 Radical Formation Mechanisms.- 4 Structure of Radicals from Nucleic Acids.- 4.1 Frozen Solution and Dry State.- 4.1.1 Radiolysis of DNA in Frozen Solution.- 4.1.2 Radicals from Solid Nucleic Acids.- 4.2 Oriented Fibers.- 4.2.1 The Wet Spinning Method.- 4.2.2 ESR Results.- 5 Radical Yields.- 5.1 General Aspects.- 5.2 Yields in Constituents.- 5.2.1 Solid Bases, Nucleosides and Nucleotides.- 5.2.2 Influence of Environmental, Parameters.- 5.2.2.1 Temperature.- 5.2.2.2 Crystallinity.- 5.2.2.3 Glasses.- 5.3 Yields in Nucleic Acids.- 5.3.1 Influence of Environmental Parameters.- 5.3.1.1 Effect of Moisture Content.- 5.3.1.2 Effect of Molecular Weight.- 5.3.1.3 Yields at Room Temperature.- 5.3.1.4 Effect of Temperature.- 5.3.1.5 Glasses 9.- 5.3.2 Comparison with Yields in Constituents.- 6 Radiomimetic Radical Production.- 6.1 Introduction.- 6.2 Interaction with H-Atoms and OH-Radicals.- 6.2.1 Addition and Abstraction Reactions with Nucleic Acid Bases and Sugars.- 6.2.2 Reactions with Nucleic Acids.- 6.3 Reaction with Electrons.- 6.3.1 ESR Characteristics of the Pyrimidine and Purine Anion Radicals.- 6.3.1.1 Pyrimidine Derivatives.- 6.3.1.2 Purine Derivatives.- 6.3.2 Conversion of the Anion Radicals.- 6.3.2.1 Pyrimidine Base Anions as Precursors of H-Addition Radicals.- 6.3.2.2 Dehalogenation Radicals in 5-Halouracils.- 6.3.2.3 Protonation Reactions of Purine Anions.- 6.4 Interaction with Excited Inert Gases.- 6.4.1 Purine and Pyrimidine Derivatives.- 6.4.2 DNA.- 6.4.3 Mechanisms of Radical Formation.- 7 Transfer Phenomena.- 7.1 Introduction.- 7.2 Substituent Effects.- 7.2.1 Barbituric Acid and Derivatives.- 7.2.2 5-Halogen-Substituted Uracil Bases and Nucleosides.- 7.3 Electron Transfer in ?-Irradiated DNA.- 7.3.1 Preliminary ESR Experiments on ?-Irradiated DNA.- 7.3.2 Mechanical Mixtures and Molecular Complexes of DNA Nucleotides.- 7.3.3 A Working Hypothesis for Internucleo-tide Spin-Transfer Processes.- 7.3.4 Other Examples of Intermolecular Spin-Transfer Processes.- 7.3.5 Formal Analysis of ESR Spectra of Dry DNA.- 7.4 Photosensitization by Dyes in Frozen Solutions.- 7.4.1 Nature of the Photosensitizers.- 7.4.2 Free Radicals Induced in Nucleotides.- 7.4.2.1 Description and Interpretation of the ESR Spectra.- 7.4.2.2 Mechanism of Radical Formation.- 7.4.2.3 Influence of Oxygen.- 7.4.2.4 Influence of the Relative Molar Concentration of Dye and Substrate.- 7.4.2.5 Influence of Dye Aggregation.- 7.4.3 Free Radicals Induced in DNA.- 7.4.3.1 Description and Interpretation of the ESR Spectra.- 7.4.3.2 Mechanism of Formation: Anionic Stage.- 7.4.3.3 Quantitative Influence of Oxygejn and Ionic Strength.- 7.4.4 General Conclusions.- References.- Section II: Chemical Aspects.- 1 Primary Events in the Radiolysis of Aqueous Solutions of Nucleic Acids and Related Substances.- 1.1 Reactive Species in Irradiated Aqueous Systems.- 1.2 Rates of Reaction with the Primary Species.- 1.3 Intermediates in the Radiolysis of Aqueous Solutions of Nucleic Acids and Their Components.- 1.3.1 Reaction with Hydroxyl Radicals.- 1.3.1.1 Pyrimidines.- 1.3.1.2 Purines.- 1.3.1.3 Nucleosides, Nucleotides and Polynucleotides.- 1.3.2 Reaction with Hydrogen Atoms.- 1.3.3 Reaction with the Solvated Electron.- 1.3.4 Reactions of the Intermediates with Added Solutes.- 1.3.4.1 Oxygen.- 1.3.4.2 Electron-Transfer Processes.- 2 Radiation-Induced Degradation of the Base Component in DNA and Related Substances - Final Products.- 2.1 Introduction.- 2.2 Nucleic Acid Constituents in Aqueous Aerated Solutions.- 2.2.1 Free Bases.- 2.2.1.1 Thymine.- 2.2.1.2 Uracil.- 2.2.1.3 Cytosine.- 2.2.1.4 5-Bromouracil.- 2.2.1.5 Adenine.- 2.2.2 Nucleosides and Nucleotides.- 2.2.2.1 Thymidine.- 2.2.2.2 5-Bromo-2?-Deoxyuridine.- 2.2.2.3 Uridine.- 2.2.2.4 Deoxyadenosine.- 2.2.2.5 Nucleotides - Thymidylic Acid and Uridylic Acid.- 2.2.2.6 Dinucleotides - TpT.- 2.3 Nucleic Acid Constituents in Deaerated Aqueous Solutions.- 2.3.1 Free Bases.- 2.3.1.1 Thymine.- 2.3.1.2 Uracil.- 2.3.1.3 Cytosine.- 2.3.1.4 Adenine.- 2.3.2 Free Bases in the Presence of a Second Solute.- 2.3.2.1 Bases and Ethanol.- 2.3.2.2 Thymine and Radiosensitizers.- 2.3.2.3 Pyrimidine Bases and Surfactants.- 2.3.2.4 Pyrimidine Bases and Amino Acids.- 2.3.3 Nucleosides and Nucleotides.- 2.3.3.1 Thymidine.- 2.3.3.2 Purine Nucleosides and Nucleotides.- 2.4 Nucleic Acid Constituents in Solid State or in Frozen Solutions.- 2.5 DNA in Aerated and Deaerated Solutions.- 2.5.1 Modifications of the Base Moieties in the Polynucleotide Chain.- 2.5.1.1 UV Absorption and IR Spectra.- 2.5.1.2 Formic or Perchloric Acid Hydrolysis - Base Destruction.- 2.5.1.3 Peroxidation of Pyrimidines.- 2.5.1.4 Indirect Determinations of the Fairly Stable Products.- 2.5.1.5 Direct Determinations of the Fairly Stable Products.- 2.5.2 Products Released from the Polynucleotide Chain.- 2.5.2.1 3H-H2O from DNA Thymine Methyl-(3H).- 2.5.2.2 Ammonia.- 2.5.2.3 Free Bases.- 2.5.2.4 Products of Base Component Degradation - Release of Carbon Dioxide from the Thymine Fragment.- 3 Radiation-Induced Degradation of the Sugar in Model Compounds and in DNA.- 3.1 Introduction.- 3.2 Free Radical Reactions of Sugars and Sugar Phosphates.- 3.3 Sugars.- 3.3.1 2-Deoxy-D-Ribose.- 3.3.1.1 Aqueous Solutions.- 3.3.1.2 Crystalline State.- 3.3.2 D-Ribose.- 3.3.2.1 Aqueous Solution.- 3.3.2.2 Solid State.- 3.4 Sugar Phosphates.- 3.4.1 D-Ribose-5-Phosphate.- 3.4.1.1 Deoxygenated Solutions.- 3.4.1.2 Oxygenated Solutions.- 3.5 Nucleosides.- 3.5.1 Scission of the N-Glycosidic Linkage in Thymidine.- 3.5.1.1 Deoxygenated Solutions.- 3.5.1.2 Oxygenated Solutions.- 3.6 Nucleotides.- 3.6.1 Phosphate Release.- 3.6.1.1 Mononucleotides.- 3.6.1.2 Thymidine-3?,5?-Diphosphate.- 3.6.2 Scission of the N-Glycosidic Linkage.- 3.6.3 Formation of Cyclo-Nucleotides.- 3.7 DNA.- 3.7.1 Product Release from DNA and the Mechanism of Strand Breaks.- 3.7.1.1 Release of Malonaldehyde.- 3.7.1.2 Release of Sugars and Unaltered Bases.- 3.7.2 End Group Determinations on Broken DNA Strands.- 3.7.2.1 5? End Groups.- 3.7.2.2 3? End Groups.- 4 Changes in the Secondary and Tertiary Structures of DNA after Irradiation.- 4.1 Hyperchromicity and Melting Curves.- 4.2 Titration.- 4.3 Other Methods.- 4.4 Conclusions.- References.- Section III: Biological Aspects.- 1 Biological Functions of DNA and Methods of Testing.- 1.1 Introduction.- 1.2 Processes in which DNA is Involved.- 1.2.1 Semiconservative Replication.- 1.2.2 Transcription.- 1.2.3 Repair.- 1.2.4 Transformation.- 1.2.5 Transfection.- 1.3 Degrees of Difficulty of Testing DNA Functions.- 1.4 Description of Several Simple Systems.- 1.4.1 Transformation with Bacterial DNA.- 1.4.2 Transfection with Phage DNA.- 1.4.2.1 Transfection of Spheroplasts.- 1.4.2.2 Transfection of Competent Cells.- 2 Radiation Effects on the Biological Function of DNA.- 2.1 Introduction.- 2.1.1 Main Types of Lesions Induced in DNA by Ionizing Radiation.- 2.1.2 Calculation of the Number of Strand Breaks in DNA.- 2.1.2.1 Analytical Ultracentrifugation.- 2.1.2.2 Preparative Ultracentrifugation.- 2.2 Inactivation of Phage DNA.- 2.2.1 The Phage and Its Advantages.- 2.2.2 Irradiation of Nucleic Acids Isolated from Phage.- 2.2.2.1 Biological Inactivation of Single-Stranded DNA.- 2.2.2.2 Biological Inactivation of Double-Stranded DNA.- 2.2.3 Irradiation of Phage.- 2.2.3.1 Inactivation of Phages with Single-Stranded DNA 27.- 2.2.3.2 Inactivation of Phages with Double-Stranded DNA.- 2.2.4 Effect of Incorporated Radionuclides on the Biological Activity of Phage DNA.- 2.3 Irradiation Effects on the Transforming and Transfecting Activity of DNA.- 2.3.1 Biological Activity of Transforming DNA Irradiated in vivo.- 2.3.2 Transforming Activity of DNA Irradiated in vitro.- 2.3.3 Contribution of Strand Breakage, Base Damage, and Crosslinks to the Inactivation.- 2.3.4 Mathematical Interpretation of the Dose Effect Curves.- 2.3.5 Biological Activity of Irradiated Transfecting DNA.- 2.4 Irradiation Effects on Transcription.- 2.4.1 Transcription on Irradiated DNA in vitro.- 2.4.2 RNA Synthesis in Irradiated Cells.- 2.5 Irradiation Effects on DNA Replication.- 2.5.1 Introduction.- 2.5.2 Methods of Measuring DNA Replication in Cells.- 2.5.2.1 Radioactive Labelling.- 2.5.2.2 Autoradiography.- 2.5.2.3 Replication Synthesis Defined.- 2.5.3 Effect of Radiation on Uptake of Precursors into DNA.- 2.5.3.1 Bacteria.- 2.5.3.2 Mammalian Cells in Culture.- 2.5.3.3 Cells of Irradiated Animals.- 2.5.4 Influence of Mitotic Cycle on the Irradiation Effects on DNA Synthesis.- 2.5.5 Form and Interpretation of Dose-Effect Curves.- 2.5.6 Inhibition of DNA Synthesis and Cell Survival.- 2.5.7 Irradiation Effects on DNA Synthesis in vitro.- 3 Modification of Radiation Damage.- 3.1 Introduction.- 3.2 Factors Enhancing the Radiosensitivity of DNA.- 3.2.1 Phase State, Dehydration, and Temperature.- 3.2.2 Oxygen.- 3.2.3 Halo#8212; Release of Carbon Dioxide from the Thymine Fragment.- 3 Radiation-Induced Degradation of the Sugar in Model Compounds and in DNA.- 3.1 Introduction.- 3.2 Free Radical Reactions of Sugars and Sugar Phosphates.- 3.3 Sugars.- 3.3.1 2-Deoxy-D-Ribose.- 3.3.1.1 Aqueous Solutions.- 3.3.1.2 Crystalline State.- 3.3.2 D-Ribose.- 3.3.2.1 Aqueous Solution.- 3.3.2.2 Solid State.- 3.4 Sugar Phosphates.- 3.4.1 D-Ribose-5-Phosphate.- 3.4.1.1 Deoxygenated Solutions.- 3.4.1.2 Oxygenated Solutions.- 3.5 Nucleosides.- 3.5.1 Scission of the N-Glycosidic Linkage in Thymidine.- 3.5.1.1 Deoxygenated Solutions.- 3.5.1.2 Oxygenated Solutions.- 3.6 Nucleotides.- 3.6.1 Phosphate Release.- 3.6.1.1 Mononucleotides.- 3.6.1.2 Thymidine-3?,5?-Diphosphate.- 3.6.2 Scission of the N-Glycosidic Linkage.- 3.6.3 Formation of Cyclo-Nucleotides.- 3.7 DNA.- 3.7.1 Product Release from DNA and the Mechanism of Strand Breaks.- 3.7.1.1 Release of Malonaldehyde.- 3.7.1.2 Release of Sugars and Unaltered Bases.- 3.7.2 End Group Determinations on Broken DNA Strands.- 3.7.2.1 5? End Groups.- 3.7.2.2 3? End Groups.- 4 Changes in the Secondary and Tertiary Structures of DNA after Irradiation.- 4.1 Hyperchromicity and Melting Curves.- 4.2 Titration.- 4.3 Other Methods.- 4.4 Conclusions.- References.- Section III: Biological Aspects.- 1 Biological Functions of DNA and Methods of Testing.- 1.1 Introduction.- 1.2 Processes in which DNA is Involved.- 1.2.1 Semiconservative Replication.- 1.2.2 Transcription.- 1.2.3 Repair.- 1.2.4 Transformation.- 1.2.5 Transfection.- 1.3 Degrees of Difficulty of Testing DNA Functions.- 1.4 Description of Several Simple Systems.- 1.4.1 Transformation with Bacterial DNA.- 1.4.2 Transfection with Phage DNA.- 1.4.2.1 Transfection of Spheroplasts.- 1.4.2.2 Transfection of Competent Cells.- 2 Radiation Effects on the Biological Function of DNA.- 2.1 Introduction.- 2.1.1 Main Types of Lesions Induced in DNA by Ionizing Radiation.- 2.1.2 Calculation of the Number of Strand Breaks in DNA.- 2.1.2.1 Analytical Ultracentrifugation.- 2.1.2.2 Preparative Ultracentrifugation.- 2.2 Inactivation of Phage DNA.- 2.2.1 The Phage and Its Advantages.- 2.2.2 Irradiation of Nucleic Acids Isolated from Phage.- 2.2.2.1 Biological Inactivation of Single-Stranded DNA.- 2.2.2.2 Biological Inactivation of Double-Stranded DNA.- 2.2.3 Irradiation of Phage.- 2.2.3.1 Inactivation of Phages with Single-Stranded DNA 27.- 2.2.3.2 Inactivation of Phages with Double-Stranded DNA.- 2.2.4 Effect of Incorporated Radionuclides on the Biological Activity of Phage DNA.- 2.3 Irradiation Effects on the Transforming and Transfecting Activity of DNA.- 2.3.1 Biological Activity of Transforming DNA Irradiated in vivo.- 2.3.2 Transforming Activity of DNA Irradiated in vitro.- 2.3.3 Contribution of Strand Breakage, Base Damage, and Crosslinks to the Inactivation.- 2.3.4 Mathematical Interpretation of the Dose Effect Curves.- 2.3.5 Biological Activity of Irradiated Transfecting DNA.- 2.4 Irradiation Effects on Transcription.- 2.4.1 Transcription on Irradiated DNA in vitro.- 2.4.2 RNA Synthesis in Irradiated Cells.- 2.5 Irradiation Effects on DNA Replication.- 2.5.1 Introduction.- 2.5.2 Methods of Measuring DNA Replication in Cells.- 2.5.2.1 Radioactive Labelling.- 2.5.2.2 Autoradiography.- 2.5.2.3 Replication Synthesis Defined.- 2.5.3 Effect of Radiation on Uptake of Precursors into DNA.- 2.5.3.1 Bacteria.- 2.5.3.2 Mammalian Cells in Culture.- 2.5.3.3 Cells of Irradiated Animals.- 2.5.4 Influence of Mitotic Cycle on the Irradiation Effects on DNA Synthesis.- 2.5.5 Form and Interpretation of Dose-Effect Curves.- 2.5.6 Inhibition of DNA Synthesis and Cell Survival.- 2.5.7 Irradiation Effects on DNA Synthesis in vitro.- 3 Modification of Radiation Damage.- 3.1 Introduction.- 3.2 Factors Enhancing the Radiosensitivity of DNA.- 3.2.1 Phase State, Dehydration, and Temperature.- 3.2.2 Oxygen.- 3.2.3 Halo?-OH Radicals.- 3.2.3 Hydrogen-Abstraction Radicals.- 3.2.3.1 Abstraction from Pyrimidine Rings.- 3.2.3.2 Abstraction from Substituent Groups to Pyrimidines and Purines.- 3.2.4 Molecular Ion Radicals.- 3.3 Sugar-Phosphate Backbone Radicals.- 3.4 Molecular Orbital Calculations.- 3.5 Radical Formation Mechanisms.- 4 Structure of Radicals from Nucleic Acids.- 4.1 Frozen Solution and Dry State.- 4.1.1 Radiolysis of DNA in Frozen Solution.- 4.1.2 Radicals from Solid Nucleic Acids.- 4.2 Oriented Fibers.- 4.2.1 The Wet Spinning Method.- 4.2.2 ESR Results.- 5 Radical Yields.- 5.1 General Aspects.- 5.2 Yields in Constituents.- 5.2.1 Solid Bases, Nucleosides and Nucleotides.- 5.2.2 Influence of Environmental, Parameters.- 5.2.2.1 Temperature.- 5.2.2.2 Crystallinity.- 5.2.2.3 Glasses.- 5.3 Yields in Nucleic Acids.- 5.3.1 Influence of Environmental Parameters.- 5.3.1.1 Effect of Moisture Content.- 5.3.1.2 Effect of Molecular Weight.- 5.3.1.3 Yields at Room Temperature.- 5.3.1.4 Effect of Temperature.- 5.3.1.5 Glasses 9.- 5.3.2 Comparison with Yields in Constituents.- 6 Radiomimetic Radical Production.- 6.1 Introduction.- 6.2 Interaction with H-Atoms and OH-Radicals.- 6.2.1 Addition and Abstraction Reactions with Nucleic Acid Bases and Sugars.- 6.2.2 Reactions with Nucleic Acids.- 6.3 Reaction with Electrons.- 6.3.1 ESR Characteristics of the Pyrimidine and Purine Anion Radicals.- 6.3.1.1 Pyrimidine Derivatives.- 6.3.1.2 Purine Derivatives.- 6.3.2 Conversion of the Anion Radicals.- 6.3.2.1 Pyrimidine Base Anions as Precursors of H-Addition Radicals.- 6.3.2.2 Dehalogenation Radicals in 5-Halouracils.- 6.3.2.3 Protonation Reactions of Purine Anions.- 6.4 Interaction with Excited Inert Gases.- 6.4.1 Purine and Pyrimidine Derivatives.- 6.4.2 DNA.- 6.4.3 Mechanisms of Radical Formation.- 7 Transfer Phenomena.- 7.1 Introduction.- 7.2 Substituent Effects.- 7.2.1 Barbituric Acid and Derivatives.- 7.2.2 5-Halogen-Substituted Uracil Bases and Nucleosides.- 7.3 Electron Transfer in ?-Irradiated DNA.- 7.3.1 Preliminary ESR Experiments on ?-Irradiated DNA.- 7.3.2 Mechanical Mixtures and Molecular Complexes of DNA Nucleotides.- 7.3.3 A Working Hypothesis for Internucleo-tide Spin-Transfer Processes.- 7.3.4 Other Examples of Intermolecular Spin-Transfer Processes.- 7.3.5 Formal Analysis of ESR Spectra of Dry DNA.- 7.4 Photosensitization by Dyes in Frozen Solutions.- 7.4.1 Nature of the Photosensitizers.- 7.4.2 Free Radicals Induced in Nucleotides.- 7.4.2.1 Description and Interpretation of the ESR Spectra.- 7.4.2.2 Mechanism of Radical Formation.- 7.4.2.3 Influence of Oxygen.- 7.4.2.4 Influence of the Relative Molar Concentration of Dye and Substrate.- 7.4.2.5 Influence of Dye Aggregation.- 7.4.3 Free Radicals Induced in DNA.- 7.4.3.1 Description and Interpretation of the ESR Spectra.- 7.4.3.2 Mechanism of Formation: Anionic Stage.- 7.4.3.3 Quantitative Influence of Oxygejn and Ionic Strength.- 7.4.4 General Conclusions.- References.- Section II: Chemical Aspects.- 1 Primary Events in the Radiolysis of Aqueous Solutions of Nucleic Acids and Related Substances.- 1.1 Reactive Species in Irradiated Aqueous Systems.- 1.2 Rates of Reaction with the Primary Species.- 1.3 Intermediates in the Radiolysis of Aqueous Solutions of Nucleic Acids and Their Components.- 1.3.1 Reaction with Hydroxyl Radicals.- 1.3.1.1 Pyrimidines.- 1.3.1.2 Purines.- 1.3.1.3 Nucleosides, Nucleotides and Polynucleotides.- 1.3.2 Reaction with Hydrogen Atoms.- 1.3.3 Reaction with the Solvated Electron.- 1.3.4 Reactions of the Intermediates with Added Solutes.- 1.3.4.1 Oxygen.- 1.3.4.2 Electron-Transfer Processes.- 2 Radiation-Induced Degradation of the Base Component in DNA and Related Substances - Final Products.- 2.1 Introduction.- 2.2 Nucleic Acid Constituents in Aqueous Aerated Solutions.- 2.2.1 Free Bases.- 2.2.1.1 Thymine.- 2.2.1.2 Uracil.- 2.2.1.3 Cytosine.- 2.2.1.4 5-Bromouracil.- 2.2.1.5 Adenine.- 2.2.2 Nucleosides and Nucleotides.- 2.2.2.1 Thymidine.- 2.2.2.2 5-Bromo-2?-Deoxyuridine.- 2.2.2.3 Uridine.- 2.2.2.4 Deoxyadenosine.- 2.2.2.5 Nucleotides - Thymidylic Acid and Uridylic Acid.- 2.2.2.6 Dinucleotides - TpT.- 2.3 Nucleic Acid Constituents in Deaerated Aqueous Solutions.- 2.3.1 Free Bases.- 2.3.1.1 Thymine.- 2.3.1.2 Uracil.- 2.3.1.3 Cytosine.- 2.3.1.4 Adenine.- 2.3.2 Free Bases in the Presence of a Second Solute.- 2.3.2.1 Bases and Ethanol.- 2.3.2.2 Thymine and Radiosensitizers.- 2.3.2.3 Pyrimidine Bases and Surfactants.- 2.3.2.4 Pyrimidine Bases and Amino Acids.- 2.3.3 Nucleosides and Nucleotides.- 2.3.3.1 Thymidine.- 2.3.3.2 Purine Nucleosides and Nucleotides.- 2.4 Nucleic Acid Constituents in Solid State or in Frozen Solutions.- 2.5 DNA in Aerated and Deaerated Solutions.- 2.5.1 Modifications of the Base Moieties in the Polynucleotide Chain.- 2.5.1.1 UV Absorption and IR Spectra.- 2.5.1.2 Formic or Perchloric Acid Hydrolysis - Base Destruction.- 2.5.1.3 Peroxidation of Pyrimidines.- 2.5.1.4 Indirect Determinations of the Fairly Stable Products.- 2.5.1.5 Direct Determinations of the Fairly Stable Products.- 2.5.2 Products Released from the Polynucleotide Chain.- 2.5.2.1 3H-H2O from DNA Thymine Methyl-(3H).- 2.5.2.2 Ammonia.- 2.5.2.3 Free Bases.- 2.5.2.4 Products of Base Component Degradation - Release of Carbon Dioxide from the Thymine Fragment.- 3 Radiation-Induced Degradation of the Sugar in Model Compounds and in DNA.- 3.1 Introduction.- 3.2 Free Radical Reactions of Sugars and Sugar Phosphates.- 3.3 Sugars.- 3.3.1 2-Deoxy-D-Ribose.- 3.3.1.1 Aqueous Solutions.- 3.3.1.2 Crystalline State.- 3.3.2 D-Ribose.- 3.3.2.1 Aqueous Solution.- 3.3.2.2 Solid State.- 3.4 Sugar Phosphates.- 3.4.1 D-Ribose-5-Phosphate.- 3.4.1.1 Deoxygenated Solutions.- 3.4.1.2 Oxygenated Solutions.- 3.5 Nucleosides.- 3.5.1 Scission of the N-Glycosidic Linkage in Thymidine.- 3.5.1.1 Deoxygenated Solutions.- 3.5.1.2 Oxygenated Solutions.- 3.6 Nucleotides.- 3.6.1 Phosphate Release.- 3.6.1.1 Mononucleotides.- 3.6.1.2 Thymidine-3?,5?-Diphosphate.- 3.6.2 Scission of the N-Glycosidic Linkage.- 3.6.3 Formation of Cyclo-Nucleotides.- 3.7 DNA.- 3.7.1 Product Release from DNA and the Mechanism of Strand Breaks.- 3.7.1.1 Release of Malonaldehyde.- 3.7.1.2 Release of Sugars and Unaltered Bases.- 3.7.2 End Group Determinations on Broken DNA Strands.- 3.7.2.1 5? End Groups.- 3.7.2.2 3? End Groups.- 4 Changes in the Secondary and Tertiary Structures of DNA after Irradiation.- 4.1 Hyperchromicity and Melting Curves.- 4.2 Titration.- 4.3 Other Methods.- 4.4 Conclusions.- References.- Section III: Biological Aspects.- 1 Biological Functions of DNA and Methods of Testing.- 1.1 Introduction.- 1.2 Processes in which DNA is Involved.- 1.2.1 Semiconservative Replication.- 1.2.2 Transcription.- 1.2.3 Repair.- 1.2.4 Transformation.- 1.2.5 Transfection.- 1.3 Degrees of Difficulty of Testing DNA Functions.- 1.4 Description of Several Simple Systems.- 1.4.1 Transformation with Bacterial DNA.- 1.4.2 Transfection with Phage DNA.- 1.4.2.1 Transfection of Spheroplasts.- 1.4.2.2 Transfection of Competent Cells.- 2 Radiation Effects on the Biological Function of DNA.- 2.1 Introduction.- 2.1.1 Main Types of Lesions Induced in DNA by Ionizing Radiation.- 2.1.2 Calculation of the Number of Strand Breaks in DNA.- 2.1.2.1 Analytical Ultracentrifugation.- 2.1.2.2 Preparative Ultracentrifugation.- 2.2 Inactivation of Phage DNA.- 2.2.1 The Phage and Its Advantages.- 2.2.2 Irradiation of Nucleic Acids Isolated from Phage.- 2.2.2.1 Biological Inactivation of Single-Stranded DNA.- 2.2.2.2 Biological Inactivation of Double-Stranded DNA.- 2.2.3 Irradiation of Phage.- 2.2.3.1 Inactivation of Phages with Single-Stranded DNA 27.- 2.2.3.2 Inactivation of Phages with Double-Stranded DNA.- 2.2.4 Effect of Incorporated Radionuclides on the Biological Activity of Phage DNA.- 2.3 Irradiation Effects on the Transforming and Transfecting Activity of DNA.- 2.3.1 Biological Activity of Transforming DNA Irradiated in vivo.- 2.3.2 Transforming Activity of DNA Irradiated in vitro.- 2.3.3 Contribution of Strand Breakage, Base Damage, and Crosslinks to the Inactivation.- 2.3.4 Mathematical Interpretation of the Dose Effect Curves.- 2.3.5 Biological Activity of Irradiated Transfecting DNA.- 2.4 Irradiation Effects on Transcription.- 2.4.1 Transcription on Irradiated DNA in vitro.- 2.4.2 RNA Synthesis in Irradiated Cells.- 2.5 Irradiation Effects on DNA Replication.- 2.5.1 Introduction.- 2.5.2 Methods of Measuring DNA Replication in Cells.- 2.5.2.1 Radioactive Labelling.- 2.5.2.2 Autoradiography.- 2.5.2.3 Replication Synthesis Defined.- 2.5.3 Effect of Radiation on Uptake of Precursors into DNA.- 2.5.3.1 Bacteria.- 2.5.3.2 Mammalian Cells in Culture.- 2.5.3.3 Cells of Irradiated Animals.- 2.5.4 Influence of Mitotic Cycle on the Irradiation Effects on DNA Synthesis.- 2.5.5 Form and Interpretation of Dose-Effect Curves.- 2.5.6 Inhibition of DNA Synthesis and Cell Survival.- 2.5.7 Irradiation Effects on DNA Synthesis in vitro.- 3 Modification of Radiation Damage.- 3.1 Introduction.- 3.2 Factors Enhancing the Radiosensitivity of DNA.- 3.2.1 Phase State, Dehydration, and Temperature.- 3.2.2 Oxygen.- 3.2.3 Halogena ted Base Analogs.- 3.2.4 Chemical Compounds Acting on Radiation Induced DNA Transients.- 3.2.5 Chemical Compounds Combining with DNA Independently of Radiochemical Reactions.- 3.3 Sulfhydryl Compounds and Radioprotection by Radical Scavenging.- 4 Repair Processes for Radiation-Induced DNA Damage.- 4.1 Introduction.- 4.2 Repair of Single-Strand Breaks in Bacteria.- 4.2.1 Measurement of Single-Strand Breaks.- 4.2.2 Different Rejoining Processes.- 4.2.3 Slow Repair in Escherichia coli.- 4.2.3.1 Genetic Control.- 4.2.3.2 Effects of Post-Irradiation Conditions.- 4.2.4 Fast Repair in E. coli.- 4.2.5 Rejoining of SSBs in Other Bacteria.- 4.2.6 Post-Irradiation Degradation.- 4.3 Rejoining of Single-Strand Breaks in Eucaryotic Cells.- 4.3.1 Introduction.- 4.3.2 End Groups Produced.- 4.3.3 Efficiency of Break Production.- 4.3.4 Rejoining after High Doses in Cultured Cells.- 4.3.4.1 Rejoining in Different Cells.- 4.3.4.2 Effects of Inhibitors.- 4.3.4.3 Energy Requirements.- 4.3.5 Studies Using Low Doses ( and DNA Content of the Genome.- 5.3 Open Questions.- 5.4 Conclusion.- 6 Conclusions and Perspectives.- References.- 1. Dose Units.- 1.1 Exposure.- 1.2 Absorbed Dose.- 1.3 Conversion Factors.- 1.4 Radiation-Chemical Yield (G-Value).- 2. List of Abbreviations.- 2.1 Chemical Names.- 2.2 Experimental and Theoretical Methods.- 2.3 Symbols, Entities and Units.
| Reihe/Serie | Molecular Biology, Biochemistry and Biophysics / Molekularbiologie, Biochemie und Biophysik ; 27 |
|---|---|
| Co-Autor | G. Ahnstrom |
| Mitarbeit |
Chef-Herausgeber: A. J. Bertinchamps |
| Zusatzinfo | biography |
| Verlagsort | Berlin |
| Sprache | englisch |
| Gewicht | 790 g |
| Themenwelt | Naturwissenschaften ► Biologie ► Biochemie |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| ISBN-10 | 3-540-08542-4 / 3540085424 |
| ISBN-13 | 978-3-540-08542-3 / 9783540085423 |
| Zustand | Neuware |
| Haben Sie eine Frage zum Produkt? |
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