Molecular and Cellular Radiobiology Project Title: Mechanisms of Action of Free Radicals and Hormones 14, Scope: (Cont'd.) RX-03-02-(c) In studies on hormone actions mild and versatile methods of solid phase peptide synthesis are developed, These methods, based on previous studies in peptide hormone chemistry, physiology, and pharmacology, allow for preparation of sophisticated peptide hormone analogs for use in research and in chemotherapy. B) Supplement to 200 Word Summary: Free radicals are essential components in many bioenergetic mechanisms. Despite the development of a substantial understanding of free radical reactions in physical-organic and polymer chemistry, the elaboration of general theories of free radical behavior in physiological chemistry and the documentation of special free radical intermediates remain patchy and incomplete. The need to detect small numbers of free radicals in biomedical experimentation has led to the widespread application of electron paramagnetic resonance (EPR) spectrometry, because EPR and related magnetic resonance techniques can identify and describe free radicals with great sensitivity and specificity, Its absolute sensitivity is often insufficient, however to detect the low residual levels of free radicals persisting in surviving tissues. The BNL program investigating bioenergetic free radical mechanisms has utilized EPR and a special high-velocity flow apparatus for maintaining steady states of labile free radicals in liquid reaction systems. Computerization, . new radical-trapping procedures, ion-irradiation techniques, and special means of examining large samples of frozen tissue have been explored. Application ‘ of ELDOR (ELectron-electron DOuble Resonance) to biomedical and irradiated samples is about to begin, ENDOR (Electron-Nuclear DOuble Resonance) applications are planned. Also, collaboration is planned with the Physics and Chemistry —~ Departments to carry out EPR spectroscopy while samples are being irradiated by an electron beam from the Dynamitron accelerator. One project is directed toward radiation and radiomimetic chemical reactions on bilogical target molecules: correlations with reactions of pollutants and carcinogens, This involves EPR studies of gamma irradiation and atom bombardment of nucleic acid constituents and identification of some hydrogen-addition and -abstraction radicals, using both amorphous and polycrystalline dry samples and some single crystals of nucleic acid bases and related compounds, Hydroxyl radicals formed by chemical reduction of hydrogen peroxide will be employed in special flow apparatus developed at BNL for high fre wey EPR (35 GHz, Q-band). Extension from radiation-like reaction on base wcleosides, etc. to oligonucleotides and possible to polynucleotides and mic acids is foreseen. Other anticipated extensions include: i) Applicatt of ELDOR and ENDOR co irradiated biochemicals in the solid state; ii) Projection of the EPR/flow work to include interactions of free radicals of some carcinogens and pollutants and of peroxy compounds with nucleic acids and their constituents and with cell membranes and their Lipid components; iii) EPR observation of radiation-produced free radicals in liquid and tissue (See Continuation Sheet) 1119291 RX- 237