Overview of symposium: Chemical mechanisms in radioprotection

Abstract

My brief is to discuss some of the facts that have emerged concerning chemical mechanisms of radioprotection. Like Dr. Phillips, I shall draw not only on information provided by speakers at this Symposium, but also, where appropriate, on information already available in the literature-information that is often overlooked by builders in their search for new principles. I shall not attempt to review each of the relevant papers presented: the authors make their 'own cases much better than I can anyway. I intend to confine my remarks to what I consider to be some important general principles. There is now a fascinating ring of reality in the progress towards a useful--and usable-radioprotector. The concepts of substances that influence immunological response, the induction of repair proteins, and the biological modifiers, all open up new areas of enquiry and illustrate clearly to me that the field of radioprotection is now undergoing a rapid metamorphosis. This Symposium is indeed timely. Dr. Phillips has made an interesting distinction between physiological and pharmacological mechanisms involving, for example, modification of radiation injury by exogenous substances, particularly those containing thiols. This is a useful and valid approach. To complement this, I shall address the problem from the standpoint of basic radiation chemical mechanisms, often flee radical in origin, and I shall certainly draw heavily on information derived from both chemical and biological studies with exogenous thiols. Of necessity, however, I must consider some aspects that Dr. Phillips alluded to in his first class of physiological mechanisms. I refer to the influence of changes in cellular levels on overall radiation damage, the interaction of sensitization and thiol protection, and the methods of influencing the yield of radiation-induced chemical lesions. Despite the current diversification in the radioprotector field, the study of substances that permit chemical repair of free radical radiation remains the major area of enquiry at all levels of biological complexity. The so-called oxygen fixation competition model first proposed over 30 years ago remains very much in vogue and figured prominently in several papers in this Symposium. The postulates that a free radical lesion induced by radiation (reaction 1) in a biologically important molecule, DNA for example, can be repaired by hydrogen transfer from appropriately located intercellular thiols (reaction 2). This reaction competes with an oxidation reaction in which f ixes the radical by peroxy-radical formation (reaction 3).