King L C, Ball L M, Jackson M, Inmon J P, Lewtas J
Toxicol Appl Pharmacol. 1986 Feb;82(2):292-300. doi: 10.1016/0041-008x(86)90204-8.
The metabolism of 1-nitro[14C]pyrene (14C-1-NP; 8.1 microM) was studied in cultured (20 hr) rabbit alveolar macrophages, lung tissue, and tracheal tissue. Metabolites from the incubation medium and from the macrophages and respiratory tract tissues were extracted and then analyzed and quantified by high-pressure liquid chromatography. The following metabolites were detected in the lung and tracheal tissue incubation medium: 1-nitropyrene-4,5-dihydrodiol, N-acetyl-1-aminopyrene, 1-aminopyrene, and 10-hydroxy-1-nitropyrene. Nitropyrene phenols (4-, 5-, 6-, 8- or 9-hydroxy-1-nitropyrene) and 3-hydroxy-1-nitropyrene were only detected in the lung and tracheal tissue and not in the incubation medium for these tissues. Minor amounts of 1-aminopyrene and 10-hydroxy-1-nitropyrene were detected in the macrophage incubation medium, and only minute quantities of 1-nitropyrene-4,5-dihydrodiol, 1-aminopyrene, and 10-hydroxy-1-nitropyrene were detected in macrophages. The total percentage of 1-NP metabolism was significantly greater in the lung and tracheal tissue (28.0 and 23.0% of the recovered 14C, respectively) than in the alveolar macrophages (6.3% of the recovered 14C). The tracheal tissue was found to have the highest activity both in 1-NP metabolism and intracellular metabolite concentration. A major portion of the 1-NP metabolites produced was released into the incubation medium. The majority of the metabolites produced by tracheal and lung tissue, 70 and 84%, respectively, were ethyl acetate extractable. The metabolites retained within the cells or tissues were also predominantly ethyl acetate extractable rather than water soluble (83% for the macrophages and trachea, 95% for the lung tissue). The metabolite profiles obtained demonstrate that metabolism by both nitro reduction and ring oxidation occurs in respiratory tissue, and a degree of tissue specificity in the formation of metabolites exists. Ring oxidation was demonstrated in the lung and tracheal tissue, but very little occurred in the macrophages.
研究了1-硝基[¹⁴C]芘（¹⁴C-1-NP；8.1微摩尔）在培养（20小时）的兔肺泡巨噬细胞、肺组织和气管组织中的代谢情况。从孵育培养基以及巨噬细胞和呼吸道组织中提取代谢产物，然后通过高压液相色谱进行分析和定量。在肺和气管组织孵育培养基中检测到以下代谢产物：1-硝基芘-4,5-二氢二醇、N-乙酰-1-氨基芘、1-氨基芘和10-羟基-1-硝基芘。硝基芘酚（4-、5-、6-、8-或9-羟基-1-硝基芘）和3-羟基-1-硝基芘仅在肺和气管组织中检测到，而在这些组织的孵育培养基中未检测到。在巨噬细胞孵育培养基中检测到少量的1-氨基芘和10-羟基-1-硝基芘，在巨噬细胞中仅检测到微量的1-硝基芘-4,5-二氢二醇、1-氨基芘和10-羟基-1-硝基芘。1-NP的总代谢百分比在肺和气管组织中（分别为回收的¹⁴C的28.0%和23.0%）显著高于肺泡巨噬细胞（回收的¹⁴C的6.3%）。发现气管组织在1-NP代谢和细胞内代谢物浓度方面均具有最高活性。产生的1-NP代谢产物的大部分释放到孵育培养基中。气管和肺组织产生的代谢产物中，分别有70%和84%可被乙酸乙酯萃取。保留在细胞或组织内的代谢产物也主要是可被乙酸乙酯萃取的，而非水溶性的（巨噬细胞和气管为83%，肺组织为95%）。所获得的代谢产物谱表明，呼吸组织中通过硝基还原和环氧化进行的代谢均会发生，并且在代谢产物形成方面存在一定程度的组织特异性。环氧化在肺和气管组织中得到证实，但在巨噬细胞中很少发生。
