Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses.
Assessment of the disposition of chiral polychlorinated biphenyls in female mdr 1a/b knockout versus wild-type mice using multivariate analyses.
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DOI：
10.1016/j.envint.2009.10.007
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发表时间：
2010-11
影响因子：
11.8
通讯作者：
Kania-Korwel, Izabela
中科院分区：
文献类型：
--
作者：
Milanowski, Bartlomiej;Lulek, Janina;Lehmler, Hans-Joachim;Kania-Korwel, Izabela
关键词：
多氯联苯（PCB）作为复杂的混合物存在于环境中，这使得识别可能受到主动迁移过程影响的PCB同源物具有挑战性。在这里，我们采用了转基因小鼠模型结合多变量分析，以调查如果手性PCBs 91，95，132，136，149，174，176和183受到多药耐药（MDR）转运的主动（对映选择性）运输。将含有这些同系物的合成PCB混合物口服给雌性FVB或mdr 1a/1b敲除小鼠。由于手性多氯联苯同系物的半衰期较短，24小时后对小鼠实施安乐死，并测定选定组织和排泄物中的多氯联苯浓度和对映体分数。主成分分析没有显示野生型和mdr 1a/1b基因敲除小鼠之间的差异。然而，Hotelling T2-测试显示，在mdr 1a/1b基因敲除小鼠的脂肪组织中，PCB浓度显着降低，对映体富集更明显。这些差异是由于mdr 1a/1b基因敲除小鼠的体重和粪便脂肪含量较高。对PCBs 91、95、136、149和174的对映体组分的分析表明，野生型和mdr 1a/1b基因敲除小鼠中所有五种同系物的对映体富集显著。总体而言，通过研究多氯联苯混合物在转基因小鼠模型结合多元数据减少的方法，PCBs 91，95，136，149和174可以排除作为底物的多药耐药性转运蛋白1a/B。
Polychlorinated biphenyls (PCBs) are present in the environment as complex mixtures, which make it challenging to identify PCB congeners that may be subject to active transport processes. Here we employ a transgenic mouse model in combination with multivariate analyses to investigate if chiral PCBs 91, 95, 132, 136, 149, 174, 176 and 183 are subject to active (enantioselective) transport by multidrug resistance (MDR) transporters. A synthetic PCB mixture containing these congeners was administered orally to female FVB or mdr1a/1b knockout mice. Due to the short half-life of chiral PCB congeners, mice were euthanized after 24 hours and PCB concentrations and enantiomeric fractions were determined in selected tissues and excreta. Principal component analysis did not reveal differences between wild-type and mdr1a/1b knockout mice. However, Hotelling T2-test revealed significantly lower PCB concentrations and a more pronounced enantiomeric enrichment in the adipose tissue of mdr1a/1b knockout mice. These differences are due to higher body weights and higher fecal fat contents of mdr1a/1b knockout mice. Analysis of the enantiomeric fractions of PCBs 91, 95, 136, 149 and 174 showed a significant enantiomeric enrichment for all five congeners in wild-type and mdr1a/1b knockout mice. Overall, by studying a PCB mixture in a transgenic mouse model in combination with a multivariate data reduction approach, PCBs 91, 95, 136, 149 and 174 could be excluded as substrates of multidrug resistance transporters 1a/b.
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