Biological Studies of Materials Arising from Energy Operations Free Radical Studies on Mechanisms of Action 14. Scope: RX-03-06- (a) of Pollutants Project Title: (Cont'd.) Nicrices, which can be formed from nitrates by soil bacteria, may be converted by stomach acids to nitrosamines, some of which can be highly mutagenic, In addition, EPR signals of presently unknown significance have been found in tissues and cells exposed to relatively high levels of nitrite and/or nitrate in their water supplies, Although once again this suggests the possibility of an EPR assay of "“effective'' biological exposure, it may also have functional consequences in terms of cancer induction by other chemicals, For example, high levels of dietary nitrace enhance EPR signal amplitude but decrease tumor incidence (i.e,, a protective effect) when given to animals exposed to various carcinogens, Clearly these preliminary findings should be followed up, and the EPR capabilities at BNL are well suited to this work, oN ‘ 15. Relationship to Other Projects: NMR studies are planned in the Biology Department, Radiation techniques to provide kinetic information and further identification of reaction intermediates are in progress in the Chemistry Department (pulse radiolysis) and in the Physics Department (on-line EPR at the Dynamitron electron accelerator), 16. Technical Progress in FY 1973: Project not yet initiated, 17. Expected Results in FY 1974: Project to be initiated in FY 1975, 18. Expected Results in FY 1975: Present programs may be extended to include consideration of non- nuclear pollutants with minimum additional support. Optimum implementation of the research activities noted would require an estimated addition of two scientific staff members and two technicians (plus one scientist and one technician associated with the radiation /EPR collaborative project). Stagged-flow and temperature-jump analyses of free radical reactions would e another technician, e reaction of several classes of known carcinogens (aminonitro- quinolines, benzanthracene-benzpyrene, nitrosamines) with DNA constituents (bases, nucleosides, nucleotides, oligonucleotides) will be examined by EPR to determine whether or not combination occurs in. the same way that radiation-produced free radicals combine, (See Continuation Sheet) 1419326 RX- 383