Research is directed toward understanding the mechanisms of toxicity of selected bioenvironmental chemicals, especially halocarbons, a major class of bioenvironmental contaminants that ultimately pose human health hazards. With an interdisciplinary basis for the research, the main research objectives include: 1. Structural identification and quantitation by mass spectrometry of certain electrophilic bioenvironmental pollutants, especially aromatic halocarbons, that utilizes recent findings about mechanisms of fragmentation which are common between photochemical and mass spectral events for polyhaloarenes. 2. Elucidation of the mechanistic pathways for the photochemical transformations of environmentally significant polyhaloarenes and the application of the mechanistic conclusions to the development of an understanding of the transformation and creation of toxic components in the environment and to the development of new methods of toxic waste disposal. 3. Investigation of the biochemical and molecular mechanisms underlying alterations in T cell activation induced by the aromatic halocarbon 2,3,7,8--tetrachlorodibenzo--p--dioxin and the elucidation of the relationship between altered T cell activation and altered immune function. 4. Determination, definition, and elucidation of the cellular and in vivo events that are important in the toxicity of glutathione conjugates of saturated aliphatic halocarbons and bisulfites and the corresponding protein thiol adducts. Much remains to be understood about environmental chemicals as individual compounds and as components of complex mixtures. The proposed research, while focusing on pure isomers of halocarbons and bisulfite, should provide much needed information on the contributions of these chemicals to the toxic effects of environmental chemicals. The four proposed projects are highly interdisciplinary; current program investigators will continue existing collaborations and, in the next grant period, will increase their total efforts to answer major questions about the chemical and biological properties of environmental chemicals. The findings will be utilized (a) for new analytical methods that are needed to establish the fates of halocarbons in the bioenvironment, (b) for development of practical procedures for photo-destruction of bioenvironmental halocarbon waste, and (c) to provide an improved basis for prediction of risks associated with human exposure to halocarbons and bisulfite.
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