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.
Table of ContentsI - The Interdisciplinary Approach to Radiation Action.- Mechanisms of Radiation Action on DNA in Model Systems - Their Relevance to Cellular DNA.- Biophysical Models of Radiation Action - Development of Simulation Codes.- Links between Radiation Track Structure, Radiochemical Species, and Cell Survival.- A Kinetic Investigation of the Mechanisms of Radiation-Induced Strand Breakage in DNA Model Systems.- Discussion Summary.- II - Cellular DNA Strand Breakage.- Measurement of DNA Double Strand Breaks in Mammalian Cells: Comparison between Pulsed Field Gel Electrophoresis and Non-Unwinding Filter Elution.- A Mouse Lymphoma Line that Undergoes Rapid Interphase Death (Apoptosis) shows Extreme Sensitivity to Radiation-Induced DNA Double-Strand Breakage.- The Influence of Genome Structural Organization on DNA Damage and Repair in Eukaryotic Cells exposed to Ionizing Radiation.- The Lethality of Radiation-Induced DNA Double-Strand Breaks for Radiations of Differing LET.- 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.- Discussion Summary.- III - Early Chemical Events in DNA Damage.- The Role of Radiation Induced Charge Migration with DNA: ESR Studies.- Early Chemical Events in the Development of Radiation Damage of DNA - Novel Approaches.- Initial Sites of One Electron Attachment in DNA.- Molecular Orbital Calculations on DNA Base Pairs.- Role of Energy and Charge Transfer in DNA Damage by Densely Ionizing Radiation.- Discussion Summary.- IV - Development of Radiation Models.- Concepts of Microdosimetry and their Applicability to DNA Studies.- The Application of Biophysical Models to Cellular DNA Damage.- The Application of Chemical Models to Cellular DNA Damage.- What Basis for the Development of Radiation-Induced DNA Damage?.- Stochastic Methods in Radiation Chemical Kinetics.- V - Chemical Mechanisms of Dose Modifiers.- The Effect of Environment upon DNA Free Radicals.- Chemical Reactivity of DNA Radicals - A Reflection of their Redox Properties.- Chemical Properties of ‘Radiation Modifiers’ of DNA Damage and their Radiobiological Effects.- Transformation Reactions of Two Isomeric OH-Adducts of 2?-Deoxyguanosine.- The Rates of the Reaction of Thiols with Radicals Derived from OH Attack on Polymeric Nucleic Acids and on DNA.- Discussion Summary.- VI - RBE from Theory to Experimental.- Models to Link DNA Damage to RBEs for Final Cellular Effects.- Repair of DNA Damage and its Effect on RBE - An Experimental Approach.- DNA Double-Strand Break Induction in Yeast by Heavy Ion Irradiation.- The Use of DNA Precipitation Assay for Evaluating DSB Induced by High and Low LET Radiations: Comparison with Sedimentation Results.- Discussion Summary.- VII - Timescale for Development of DNA Damage.- The Development of Chemical Damage of DNA in Aqueous Solution.- Radical Multiplicity in Radiation-Induced DNA Strand Breaks: Implications for their Chemical Modification.- Effect of Dose Modifiers on Radiation-Induced Cellular DNA Damage.- Oxygen Enhancement of Radiosensitivity and Nuclear GSH Content.- Discussion Summary.- VIII - LET and Chromosomal Damage.- Primary Damage and Fixation of Chromosomal DNA as probed by Monochromatic Soft X-rays and Low-Energy Neutrons.- Chromosomal Damage in Human Lymphocytes: Effect of Radiation Quality.- Heavy-Ion Induced Chromatin Damage and Repair: PCC and Chromosome Painting.- Discussion Summary.- IX - Additional Short Presentations.- Radical Oxidation of the Purine Moieties of DNA and Related Nucleosides.- Radical-Induced Base Damage in Aqueous DNA Solutions.- Primary and Secondary Radicals in Thymine Derivatives: Solid State ESR/ENDOR Study of 1-Me-Thymine and Thymidine.- Radiation Effects on Transcription in Cells and Isolated Cell Nuclei.- X - Workshop Summaries.- Summary Comments from a Physicist.- Summary from a Chemist’s Point of View.- Summary of the Workshop from the View of a Biologist.