Biological Studies of Materials Arising from Energy Operations Free Radical Studies on Mechanisms of Action Project Title: of Pollutants RX-03-06- (a) 14, Scope: (Cont'd,) organism is initially exposed. Hence the biological significance of EPR findings regarding the potential toxicity of pollutants would be heightened if host-mediated assays were employed, using appropriate implantations of agents in animals to permit biotransformations (whether activating or detoxifying) to take place. EPR surveys of implants or host tissues themselves would allow the possibility of developing an in situ or in vivo EPR assay for pollutant carcinogenicity or mutagenicity to be evaluated,| Nitrogen oxides are among the volatile products of combustion of fossil fuels (as well as of tobacco smoke), and their atmospheric photochemistry is responsible for most of the color and much of the recog- nized biological irritation due to photochemical smogs. As oxidizing chemicals, some even being free radicals (e.g., nitric oxide), radidmimetic character might be anticipated, possibly including long-range effects such as carcinogenesis or mutagenesis. However, Little documentation is in hand regarding the distribution, reactions and biological fate of nitrogen oxides or the other atmospheric oxidants associated with fuel combustion, such as ozone, EPR and related double resonance spectroscopies have the potential to analyze from biological samples (including cells and tissues) the para- magnetic centers that are formed by the association of nitrogen oxides with hemoglobin and with other heme proteins (especially cytochromes), as well as more stable free radicals (such as lipoperoxides) that may be produced by the reactions of radiation, nitric oxiden, ozone, etc,, with lipids and biological membranes, In fact a crude EPR survey some years ago reported the generation of paramagnetic sites in distant tissues of animals that breathed air containing various combustion products, including nitrogen oxides, : . The special capability of the BNL bioenergetic program involving free radicals to carry out EPR and double resonance measurements on tissue samples could readily be extended to monitor the attack of ozone and nitrogen oxides in intact animals, Additional studies on cells, their components, and on biochemicals would complement the work, and its inter- pretation would be further supported by accompanying microscopic and bio- chemical analyses, The possibility should be considered of using EPR technigues to develop an assay for human exposure to some of the environmenta ents of chis class. vate buildup in ground water may result from leaching that follows the strip mining of coal, as well as from sewage and fertilizers, The biological consequences have been thought to be mostly those associated with eutrophication; however, there are some indications that levels of both nitrites and nitrates in drinking water may be important to health. (See Continuation Sheet) 1119325 RX-382