The comprehensive objective of the proposed research involves the characterization of hemoglobin adducts, formed upon exposure to xenobiotics. The model class of compounds to be studied for adduct formation are aliphatic epoxides, since (1) they have been demonstrated to be intermediates in the biotransformation of several ethylenic compounds, (2) their high chemical reactivity results in covalent binding to cellular macromolecules (proteins and nucleic acids), and (3) they are widely used in industry and thus are potential health hazards for exposed workers.
The specific aims of the project are: 1) To synthesize, purify and characterize specific amino acid adducts to be used as analytical standards for in vitro and in vivo product formation. Amino acid adducts will be purified by suitable HPLC methodologies and characterized by gas chromatography/mass spectrometry and nuclear magnetic resonance.
