National Water Research Institute, Burlington, ON, Canada.
Arch Environ Contam Toxicol. 2011 Jan;60(1):116-23. doi: 10.1007/s00244-010-9539-9. Epub 2010 May 13.
Many types of pulp and paper mill effluents have the ability to induce mixed-function oxygenase (MFO) activity and vitellogenin (VTG) protein in exposed male fish. The search for the compounds responsible for MFO induction has led to several classes of compounds, among them retene and stilbenes. The objective of this study was to investigate the biological activities of candidate stilbene compounds. Three stilbenes, 3,5-dihydroxystilbene (pinosylvin; P1), 3-hydroxy-5-methoxystilbene (P2), and 3,5-dimethoxystilbene (P3), were extracted from Scotch pine (Pinus sylvestris) and purified to evaluate their ability to induce MFO activity in vitro using ethoxyresorufin-O-deethylase (EROD) activity in a rat hepatoma cell line (H4IIE). As these compounds may be chlorinated during pulp bleaching, chlorination of P2 was undertaken, producing di- and trichlorinated isomers (Cl-P2), which were also tested. Compounds were tested for EROD-inducing ability in vivo by exposing juvenile rainbow tout (Oncorhynchus mykiss) to waterborne concentrations (0.010 to 1.0 mg/L) for 4 days. Compounds were also tested for their ability to induce VTG in trout primary liver cells in vitro. The stilbenes were weak inducers of EROD and VTG. H4IIE EROD was induced by all four compounds, with the most potent induction by P3, followed by P1, the Cl-P2 mixture, and then P2. Induction for all four stilbenes was from 3.13 × 10⁻³ to 3.57 × 10⁻⁴ as potent as retene and about 1.11 × 10⁻⁵ to 1.20 × 10⁻⁶ as potent as TCDD. Juvenile rainbow trout did not show EROD induction after exposures to P1, P2, or the Cl-P2 mixture, whereas P3 caused activity fourfold above that of controls. P1, P3, and Cl-P2 all weakly induced VTG in rainbow trout hepatocytes. The most potent inducer of VTG was Cl-P2, followed by P3 and P1. The results show the ability of wood-derived stilbenes to cause weak MFO induction in fish and in rat liver cells and to weakly induce vitellogenin in fish liver cells.
许多类型的纸浆和造纸厂废水都具有诱导雄性鱼类混合功能氧化酶（MFO）活性和卵黄蛋白原（VTG）蛋白的能力。为了寻找导致 MFO 诱导的化合物，已经发现了几类化合物，其中包括瑞香醇和芪类。本研究的目的是研究候选芪类化合物的生物学活性。从苏格兰松（Pinus sylvestris）中提取了三种芪类化合物，3,5-二羟基芪（pinosylvin；P1）、3-羟基-5-甲氧基芪（P2）和 3,5-二甲氧基芪（P3），并进行了纯化，以评估它们在大鼠肝癌细胞系（H4IIE）中使用乙氧基 RESO 脱乙基酶（EROD）活性体外诱导 MFO 活性的能力。由于这些化合物在纸浆漂白过程中可能会被氯化，因此对 P2 进行了氯化，产生了二氯和三氯代同系物（Cl-P2），也对其进行了测试。通过将幼彩虹鳟（Oncorhynchus mykiss）暴露于水中浓度（0.010 至 1.0 mg/L）4 天，在体内测试化合物的 EROD 诱导能力。还在体外测试了化合物诱导鳟鱼原代肝细胞中 VTG 的能力。这些芪类化合物对 EROD 和 VTG 的诱导作用较弱。四种化合物均诱导 H4IIE EROD，其中 P3 的诱导作用最强，其次是 P1、Cl-P2 混合物，然后是 P2。所有四种芪类化合物的诱导作用均为 3.13×10⁻³至 3.57×10⁻⁴，与瑞香醇相当，约为 TCDD 的 1.11×10⁻⁵至 1.20×10⁻⁶。暴露于 P1、P2 或 Cl-P2 混合物后，幼彩虹鳟并未显示出 EROD 诱导作用，而 P3 则导致活性比对照组高四倍。P1、P3 和 Cl-P2 均弱诱导彩虹鳟肝细胞中的 VTG。诱导 VTG 作用最强的是 Cl-P2，其次是 P3 和 P1。结果表明，木材衍生的芪类化合物具有在鱼类和大鼠肝细胞中引起较弱的 MFO 诱导作用，并在鱼类肝细胞中弱诱导卵黄蛋白原的能力。
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