Biological Studies of Materials Arising from Energy Operations Project Title: 14, Scope: Free Radical Studies on Mechanisms of Action of Pollutants (Cont'd.) RX-03-06- (a) NMR cannot be applied to complex reactions as readily as can EPR, and it has much lower intrinsic sensitivity, it is capable of studying the final diamagnetic (i,e., nonparamagnetic) products of the reactions whose inter- medicate combining steps would be analyzed by EPR methods. 2) The kinds of EPR techniques to be used in the investigations of reactive free radicals are capable of providing rich detail regarding the chemical nature and properties of paramagnetic reaction intermediates, but under the circumstances envisioned the accurate quantitative data required for kinetic analyses are not usually obtainable. However knowledge of reaction kinetics can be invaluable in making rigorous interpretations of reaction mechanisms, so the value of EPR studies of pollutants could be usefully supplemented by coordinating them with kinetic studies already under way or projected for inclusion in the present BNL research program ‘studying the bioenergetics of free radicals, One current collaboration with the Chemistry Department uses stopped- flow and temperature-jump methods to analyze certain free radical reactions, With the further provision of a senior technician or postdoctoral-level scientist, this collaboration could supplement studies of free radical reactions of pollutants with kinetic measurements. Recently several research centers have recognized the great potential of using radiation methods to study certain kinds of biochemical reactions, especially oxidation-reduction reactions involving free radicals. Both radiation chemistry and pulse radiolysis approaches are applicable. At BNL a proposal is presently being developed to apply these radiation methods” to biophysical problems, and a major part of the proposal concerns the development of an experimental facility for EPR measurements on-line at an existing electron accelerator (The Dynamitron), using special EPR components already on hand (Physics Department). Collaboration between Medical, Chemistry, and Physics Departments is proposed, and a supplementary budget of $55,000/yr (plus $10,000 installation costs for the first year) is being sought, but no funds have yet been committed. The present scientific justification is directed toward problems of radiation biophysics, non- radiation biochemistry, and the correlation of free radical mechanisms between the two, However, radiation is potentially a very useful means of generating reactive free radical forms of pollutants, and pulse radiolysis Mube used co obtain important kinetic data, while the on-line radiatign/ weility would be a uniquely powerful analytical tool in research on icals of pollutants, 3) It is now recognized that the proximate forms of carcinogens and mutagens ( the forms that actually react at biological target sites ) may be significantly altered by metabolic biochemistry from those to which the (See Continuation Sheet) 1879324 RX-381