||Nitropyrene: DNA Binding and Adduct Formation in Respiratory Tissues.
Jackson, M. A. ;
King, L. C. ;
Ball, L. M. ;
Ghayourmanesh, S. ;
Jeffrey, A. M. ;
||Health Effects Research Lab., Research Triangle Park, NC. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;North Carolina Univ. at Chapel Hill. Dept. of Environmental Sciences and Engineering. ;Columbia Univ. Health Science Center, New York.
Deoxyribonucleic acids ;
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Binding of 1-nitro(14C)pyrene (NP) or its metabolites to cellular DNA and protein in cultures of rabbit alveolar macrophages, lung tissue and tracheal tissue was examined. DNA binding in tracheal tissue (136 + or - 18.3 pmol NP/mg DNA) was four to five times the levels measured in either lung tissue (38 + or - 9.4 pmol NP/mg DNA) or macrophages (26 + or - 7.5-pmol NP/mg DNA). Adduct analysis of DNA isolated from lung tissue incubated with 3H-1-nitropyrene in vitro resulted in the identification of 2-5% of the NP adducts as C8-deoxyguanosine 1-aminopyrene. NP was also bound to cellular protein in tracheal tissue and lung tissue, and at a lower level in macrophages. Co-cultivation of the macrophages with lung and tracheal tissue decreased the DNA binding in tracheal tissue by 45%. Following intratracheal instillation of diesel particles (5 mg) vapor-coated with 14C-NP (380 ppm, 0.085 microCi/mg) particles into rats, 5 to 8% of the radioactivity remained in the lungs after 20 hours. Most of the diesel particles were also deposited in the lung. Examination of DNA and protein binding in this tissue showed 5-12% of the pulmonary 14C bound to protein and no detectable levels of 14C bound to DNA.