This project involves both the utilization and continued development and integration of chromatographic, electrophoretic, and the most advanced mass spectrometric methods required in bioanalytical identification and structural elucidation studies necessary to reveal the detailed molecular nature of xenobiotic toxicity and carcinogenesis in this Program project. It is technically feasible for the first time to obtain a complete view of both DNA and protein adduction in the same tissues at environmentally relevant doses. This new information will provide crucial insight of fundamental importance to formulation of realistic and reliable methods of risk assessment. To date this program project has provided the first exciting, pioneering experiments which establish clearly that the collaborative use of the combination of AMS detection, gel electrophoresis and advanced methods of biological mass spectrometry will yield information on macromolecular target protein identity from environmentally realistic exposure doses in vivo. This information will be directly correlated with DNA adducts in the same tissues and thus provide a comprehensive view of the altered cell machinery from xenobiotic exposure to humans from Superfund sites.
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