Pothuluri J V, Evans F E, Heinze T M, Fu P P, Cerniglia C E
National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA.
J Toxicol Environ Health. 1996 Apr 19;47(6):587-99. doi: 10.1080/009841096161555.
Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are direct-acting mutagens and carcinogens that are considered a risk to human health. We investigated the metabolism of 2-nitrofluorene by the fungus Cunninghamella elegans ATCC 36112. At 144 h of incubation, C. elegans had metabolized about 81% of the [9-14C]-2-nitrofluorene, resulting in 6 metabolites. The major metabolites were separated by reversed-phase high-performance liquid chromatography and identified by 1H NMR, ultraviolet (UV)-visible, and mass spectral analyses as 2-nitro-9-fluorenol, 2-nitro-9-fluorenone, 6-hydroxy-2-nitrofluorene, and sulfate conjugates of 7-hydroxy-2-nitro-9-fluorenone and 7-hydroxy-2-nitrofluorene. 2-Nitro-9-fluorenol accounted for about 62% of the total metabolism. For comparison with the microbial system, experiments with liver microsomes of rats pretreated with 3-methyl-cholanthrene were conducted. Microsomal incubations indicated formation of phenolic and ring-hydroxylated products of 2-nitrofluorene. 2-Nitrofluorene and hydroxylated metabolites have been previously implicated as direct-acting mutagens in bacterial assays and have shown sister chromatid exchanges in vivo in bone marrow cells and in vitro in ovary cells and unscheduled DNA synthesis in mammalian studies. Previous studies with other PAHs using C. elegans have shown that the phenols and glucoside and sulfate conjugates of phenols are generally less mutagenic than the parent. The results from the metabolism of 2-nitrofluorene by C. elegans suggests the detoxification potential of this fungus.
硝化多环芳烃（硝基多环芳烃）是直接作用的诱变剂和致癌物，被认为对人类健康构成风险。我们研究了真菌雅致小克银汉霉ATCC 36112对2-硝基芴的代谢情况。在培养144小时时，雅致小克银汉霉代谢了约81%的[9-¹⁴C]-2-硝基芴，产生了6种代谢产物。主要代谢产物通过反相高效液相色谱法分离，并通过¹H NMR、紫外可见光谱和质谱分析鉴定为2-硝基-9-芴醇、2-硝基-9-芴酮、6-羟基-2-硝基芴以及7-羟基-2-硝基-9-芴酮和7-羟基-2-硝基芴的硫酸盐结合物。2-硝基-9-芴醇约占总代谢量的62%。为了与微生物系统进行比较，我们用3-甲基胆蒽预处理大鼠的肝微粒体进行了实验。微粒体孵育表明形成了2-硝基芴的酚类和环羟基化产物。2-硝基芴和羟基化代谢产物先前在细菌试验中被认为是直接作用的诱变剂，并且在体内骨髓细胞和体外卵巢细胞中显示出姐妹染色单体交换，在哺乳动物研究中显示出非预定DNA合成。先前使用雅致小克银汉霉对其他多环芳烃的研究表明，酚类及其葡糖苷和硫酸盐结合物通常比母体的诱变性小。雅致小克银汉霉对2-硝基芴的代谢结果表明了这种真菌的解毒潜力。
