The Early Effects of Radiation on DNA (Nato ASI Subseries H:, 54)

Interest in the biological effects of ionising radiation closely followed the identification of such radiation. The realisation that DNA is the site of genetic infonnation in cells subsequently focussed attention on DNA as an important target in the lethal and mutagenic effects of ionising radiation. Thus radiation effects upon DNA became an important area for fundamental scientific studies by radiation biologists, chemists and physicists. To a first approximation, the concerns of the three disciplines can be divided by time scales: the physical process of energy deposition from photon or charged 16 12 particle and subsequent relaxation (-10- to 10- secs), followed by chemical 12 2 reactions (- 10- to 10 secs), and fmally, the expression of biological effect (minutes to years). Thus, the concept of 'early processes' conveys different ideas to different scientists, although they are all interrelated. To attempt to describe in any detail all these processes is a mammoth task which is not made easier by the different conventions and experimental approaches of the three disciplines. However, the recent advances in all these scientific areas seemed, to the organisers at least, to offer the opportunity to stimulate more active interaction between physicists, chemists and biologists. With this in mind, a multi-disciplinary workshop was organised, which brought together some fifty scientists to present their own specialist interests and, through extensive discussion, explore which problems are of high priority and require input from the different disciplines to resolve them. Front Matter....Pages I-XII Mechanisms of Radiation Action on DNA in Model Systems - Their Relevance to Cellular DNA....Pages 1-16 Biophysical Models of Radiation Action - Development of Simulation Codes....Pages 17-32 Links Between Radiation Track Structure, Radiochemical Species, and Cell Survival....Pages 33-48 A Kinetic Investigation of the Mechanisms of Radiation-Induced Strand Breakage in DNA Model Systems....Pages 49-50 Discussion on Interdisciplinary Approach to Radiation Action....Pages 51-54 Measurement of DNA Double Strand Breaks in Mammalian Cells: Comparison Between Pulsed Field Gel Electrophoresis and Non-Unwinding Filter Elution....Pages 55-69 A Mouse Lymphoma Line that Undergoes Rapid Interphase Death (Apoptosis) Shows Extreme Sensitivity to Radiation-Induced DNA Double-Strand Breakage....Pages 71-84 The Influence of Genome Structural Organization on DNA Damage and Repair in Eukaryotic Cells Exposed to Ionizing Radiation....Pages 85-101 The Lethality of Radiation-Induced DNA Double-Strand Breaks for Radiations of Differing LET....Pages 103-104 Single-Strand Breaks and Base Damage in DNA of Human White Blood Cells in Full Blood Exposed to Ionizing Radiation Detected at Biologically Relevant Doses....Pages 105-106 Discussion: Cellular DNA Strand Breakage....Pages 107-110 The Role of Radiation Induced Charge Migration with DNA: ESR Studies....Pages 111-124 Early Chemical Events in the Development of Radiation Damage of DNA - Novel Approaches....Pages 125-140 Initial Sites of One Electron Attachment in DNA....Pages 141-154 Molecular Orbital Calculations on DNA Base Pairs....Pages 155-156 Role of Energy and Charge Transfer in DNA Damage by Densely Ionizing Radiation....Pages 157-158 Early Cemical Events in DNA Damage....Pages 159-162 Concepts of Microdosimetry and their Applicability to DNA Studies....Pages 163-178 The Application of Biophysical Models to Cellular DNA Damage....Pages 179-193 The Application of Chemical Models to Cellular DNA Damage....Pages 195-209 What Basis for the Development of Radiation-Induced DNA Damage?....Pages 211-212 Stochastic Methods in Radiation Chemical Kinetics....Pages 213-214 The Effect of Environment upon DNA Free Radicals....Pages 215-230 Chemical Reactivity of DNA Radicals - A Reflection of their Redox Properties....Pages 231-247 Chemical properties of ‘radiation modifiers’ of DNA damage and their radiobiological effects....Pages 249-264 Transformation Reactions of Two Isomeric OH-Adducts of 2’-Deoxyguanosine....Pages 265-266 The Rates of the Reaction of Thiols with Radicals Derived from OH Attack on Polymeric Nucleic Acids and on DNA....Pages 267-268 Radical Chemistry in Crystals, Matrices and in Aqueous Solution. Redox Properties and Proton Transfer Processes.....Pages 269-270 Models to Link DNA Damage to RBEs for Final Cellular Effects....Pages 271-286 Repair of DNA Damage and its Effect on RBE - An Experimental Approach....Pages 287-305 DNA Double-Strand Break Induction in Yeast by Heavy ION Irradiation....Pages 307-308 The Use of DNA Precipitation Assay for Evaluating DSB Induced by High and Low LET Radiations: Comparison with Sedimentation Results....Pages 309-310 Discussion of the Session on RBE from Theory to Experiment....Pages 311-315 The Development of Chemical Damage of DNA in Aqueous Solution....Pages 317-332 Radical Multiplicity in Radiation-Induced DNA Strand Breaks: Implications for their Chemical Modification....Pages 333-346 Effect of Dose Modifiers on Radiation-Induced Cellular DNA Damage....Pages 347-362 Oxygen Enhancement of Radiosensitivity and Nuclear GSH Content....Pages 363-364 Timescale for Development of DNA Damage....Pages 365-368 Primary Damage and Fixation of Chromosomal DNA as Probed by Monochromatic Soft X-rays and Low-Energy Neutrons....Pages 369-384 Chromosomal Damage in Human Lymphocytes: Effect of Radiation Quality....Pages 385-396 Heavy-Ion Induced Chromatin Damage and Repair: PCC and Chromosome Painting....Pages 397-398 Discussion Session on LET and Chromosome Damage....Pages 399-401 Radical Oxidation of the Purine Moities of DNA and Related Nucleosides....Pages 403-404 Radical-Induced Base Damage in Aqueous DNA Solutions....Pages 405-408 Primary and Secondary Radicals in Thymine Derivatives: Solid State ESR/ENDOR Study of 1-Me-Thymine and Thymidine....Pages 409-410 Radiation Effects on Transcription in Cells and Isolated Cell Nuclei....Pages 411-412 Summary Comments from a Physicist....Pages 413-416 Summary from a Chemist’s Point of View....Pages 417-420 Summary of the Workshop from the View of a Biologist....Pages 421-425 Back Matter....Pages 427-433 The latest theories and results on the early effects of radiation on DNA are presented and summarised in this text. Contributions are made by leading radiation physicists, chemists and biologists. All three subject areas have shown great advances in recent years, e.g. the computer codes and Monte Carlo calculations used by physicists, the deeper understanding of free radical intermediates by chemists, and the techniques of molecular biology. The reader will gain an insight into the different scientific languages and approaches used by physicists, chemists and biologists in the understanding of the effects of radiation on living matter