Jackson M A, King L C, Ball L M, Ghayourmanesh S, Jeffrey A M, Lewtas J
Environ Health Perspect. 1985 Oct;62:203-7. doi: 10.1289/ehp.8562203.
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 +/- 18.3 pmole NP/mg DNA) was four to five times the levels measured in either lung tissue (38 +/- 9.4 pmole NP/mg DNA) or macrophages (26 +/- 7.5 pmole NP/mg DNA). Adduct analysis of DNA isolated from lung tissue incubated with 1-nitro[H3]pyrene in vitro resulted in the identification of 2 to 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. Cocultivation 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 muCi/mg) particles into rats, 5-8% of the radioactivity remained in the lungs after 20 hr. Most of the diesel particles were also deposited in the lung. Examination of DNA and protein binding in this tissue showed 5 to 12% of the pulmonary 14C bound to protein and no detectable levels of 14C bound to DNA.
研究了1-硝基(14C)芘(NP)或其代谢产物与兔肺泡巨噬细胞、肺组织和气管组织培养物中细胞DNA和蛋白质的结合情况。气管组织中的DNA结合量(136±18.3 pmol NP/mg DNA)是肺组织(38±9.4 pmol NP/mg DNA)或巨噬细胞(26±7.5 pmol NP/mg DNA)中测量水平的四到五倍。对体外与1-硝基[H3]芘孵育的肺组织分离的DNA进行加合物分析,结果表明2%至5%的NP加合物为C8-脱氧鸟苷1-氨基芘。NP也与气管组织和肺组织中的细胞蛋白质结合,而在巨噬细胞中的结合水平较低。巨噬细胞与肺和气管组织共培养可使气管组织中的DNA结合量降低45%。将涂有14C-NP(380 ppm,0.085 μCi/mg)的柴油颗粒(5 mg)经气管内注入大鼠后,20小时后5%-8%的放射性仍留在肺中。大多数柴油颗粒也沉积在肺中。对该组织中DNA和蛋白质结合的检测表明,肺部14C的5%至12%与蛋白质结合,未检测到14C与DNA的结合水平。