Determination of in vitro relative potency (REP) values for mono-ortho polychlorinated biphenyls after purification with active charcoal
Determination of in vitro relative potency (REP) values for mono-ortho polychlorinated biphenyls after purification with active charcoal
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DOI：
10.1016/j.toxlet.2006.04.005
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发表时间：
2006-09-10
影响因子：
3.5
通讯作者：
Van den Berg, M.
中科院分区：
文献类型：
--
作者：
Peters, A. K.;Leonards, P. E.;Van den Berg, M.
二恶英类化合物的TEF系统包括对单邻位多氯联苯（MO-PCBs）的TEF值进行赋值。少量芳烃受体（AhR）活性杂质可能导致人为的较高的相对效价（REP）值。mo -多氯联苯-105、-118、-156和-167在活性炭柱上纯化，以去除可能作为杂质存在的AhR激动剂。在稳定转染含有ahr应答（AhR-EGFP）报告基因的细胞系（hlg1.1 .1c3小鼠，h4g1.1 . c2大鼠肝癌）中，研究了纯化的mo -多氯联苯对ahr依赖性基因表达的激活或抑制作用。此外，EROD活性被用作这些细胞系CYP1A1活性的标记物。MO-PCBs -105、-118、-156诱导AhR-EGFP在两种啮齿动物细胞系中的表达，其中pcbs -156 （10 μ M）效果最好；诱导的基因表达与27%的TCDD（小鼠细胞）和62.5 +/- 3.4%（大鼠细胞）相似。这与两种细胞系的EROD活性增加相一致，分别达到TCDD的20.5 +/- 1.5%和68 +/- 3.2%的最大值。PCB-167未见诱导作用。在HIG1.1c3小鼠细胞中，PCB-105、-118和-156 （10 μ M）显著降低TCDD诱导的AbR-EGFP表达，分别为TCDD的50.9 +/- 2.9%、58.3 +/- 2.2%和70.8 +/- 1.3%。与TCDD相比，EROD活性降低了39.3 +/- 2.8%，67 +/- 5%和48.3 +/- 4%。PCB-167没有显著减少。在大鼠细胞中，只有PCB-156导致tcdd诱导的AhR-EGFP表达显著下降35%，表明物种差异起了作用。我们的研究结果表明，MO-PCBs的纯化是确定准确REP值的重要步骤，并且很可能导致低于世界卫生组织目前指定的TEF值。2006爱思唯尔爱尔兰有限公司版权所有。
The TEF system for dioxin-like compounds has included assignment of TEF values for mono-ortho polychlorinated biphenyls (MO-PCBs). Small traces of aryl hydrocarbon receptor (AhR)-active impurities could result in artifactually higher relative potency (REP) values. MO-PCBs -105, -118, -156, and -167 were purified on an active charcoal column to remove AhR agonists that could be present as impurities. Activation or inhibition of AhR-dependent gene expression by purified MO-PCBs was studied in stably transfected cell lines (HlG1.1c3 mouse, H4G1.1c2 rat hepatoma), containing an AhR-responsive (AhR-EGFP) reporter gene. In addition, EROD activity was used as marker for CYP1A1 activity in these cell lines. MO-PCBs -105,-118,-156 induced AhR-EGFP expression in both rodent cell lines, with PCB-156 (10 mu M) being most effectively; inducing gene expression to similar to 27% of TCDD (mouse cells) and 62.5 +/- 3.4% (rat cells) of TCDD. This concurred with increased EROD activity in both cell lines to maxima of 20.5 +/- 1.5% and 68 +/- 3.2% of TCDD, respectively. No induction was observed for PCB-167. In the HIG1.1c3 mouse cells, PCB-105, -118 and -156 (10 mu M) significantly reduced TCDD-induced AbR-EGFP expression to 50.9 +/- 2.9%, 58.3 +/- 2.2% and 70.8 +/- 1.3% of TCDD. Reduced EROD activity was also observed, of 39.3 +/- 2.8%, 67 +/- 5% and 48.3 +/- 4% compared to TCDD. PCB-167 did not result in significant reduction. In rat cells, only PCB-156 resulted in significant decrease in TCDD-induced AhR-EGFP expression of 35%, suggesting species differences play a role. Our results suggest that purification of MO-PCBs is an essential step in determining accurate REP values, and could very likely lead to lower TEF values than those presently assigned by the WHO. (c) 2006 Elsevier Ireland Ltd. All rights reserved.