One of the major research concerns at NIEHS is to understand the interactions between exogenous chemicals and biomolecules within the body. For a complete understanding of this interaction, the structures of the products of covalent interactions must be elucidated. Of special concern are the products of reactions between environmental carcinogens and DNA. As model systems, we are currently studying the in vitro interactions between 3-nitrofluorene and calf thymus DNA and between AZQ and quanosine. 3-Nitrofluorene must be reduced to the reactive hydroxylamine intermediate before it can react with DNA. This reductive interaction has been carried out in vitro using both chemical reduction and biologically mediated reduction (xanthine oxidase). The structure of the modified nucleoside isolated from the reaction has been elucidated by the use of a combination of FAB/MS and FAB/MS-MS and determine to be N- (deoxyguanosin- 8-yl)-3-aminofluoranthene. The analysis of the reaction of AZQ with quanosine has been initiated. An adduct has been isolated and tentatively identified. The final structure proof is currently in progress.
