||Metabolism and DNA Binding of 1-Nitro 14C Pyrene by Isolated Rabbit Tracheal Epithelial Cells.
King, L. C. ;
Jackson, M. ;
Ball, L. M. ;
Lewtas, J. ;
||Health Effects Research Lab., Research Triangle Park, NC. ;North Carolina Univ. at Chapel Hill. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.
Cultured cells ;
Laboratory animals ;
Aromatic polycyclic hydrocarbons ;
Nitro compounds ;
Protein binding ;
DNA adducts ;
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The metabolism of 1-nitro(14C)pyrene (1-NP) and the binding of its reactive intermediates to DNA and protein was examined in rabbit tracheal epithelial cells. The predominant metabolites identified and quantified in the medium were the ring oxidation products, a 1-NP-Diol, 1-NP phenols (6- or 8-OH-1-NP, 10-OH-1-NP, and 3-OH-1-NP). Major metabolites formed by nitroreduction were N-acetyl-1-aminopyrene and 1-aminopyrene. The rate of both 1-NP metabolism and DNA binding was very high in these tracheal cells. The high rate of 1-NP metabolism and DNA binding suggests that tracheal cells may be a target tissue for tumor induction by nitro-PAHs associated with diesel and other combustion particle emissions. The preponderance of highly mutagenic 1-NP phenols as metabolites suggests that ring oxidation as well as nitroreduction may result in intermediates which form DNA adducts.