In Vitro Assay Shows That PCB Metabolites Completely Saturate Thyroid Hormone Transport Capacity in Blood of Wild Polar Bears (Ursus maritimus)
In Vitro Assay Shows That PCB Metabolites Completely Saturate Thyroid Hormone Transport Capacity in Blood of Wild Polar Bears (Ursus maritimus)
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DOI：
10.1021/es903029j
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发表时间：
2010-04-15
影响因子：
11.4
通讯作者：
Legler, Juliette
中科院分区：
文献类型：
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作者：
Gutleb, Arno C.;Cenijn, Peter;Legler, Juliette
持久性化学品由于其化学反应性和物理化学特性而在北极环境中积累，多氯联苯是北极熊体内最集中的污染物类别。多氯联苯和多溴联苯醚（PBDE）阻燃剂的代谢会改变其毒理学特性，已知这些代谢物会干扰啮齿动物和人类甲状腺激素（TH）与甲状腺素运载蛋白（TTR）的结合。在北极熊血浆样品中，孵育和PAGE分离后未观察到[（125）I]-T（4）与TTR的结合。用（（14）C）-4-OH-CB 107（一种比内源性配体T（4）对TTR具有更高结合亲和力的化合物）孵育血浆样品，导致竞争性结合，如凝胶中出现放射性标记的TTR峰所证明的。血浆与T（4）孵育高达1 mM，一个浓度，不再是生理相关的没有导致任何可见的竞争。这些结果表明野生北极熊TTR上T（4）的结合位点是完全饱和的。结合位点的这种饱和可以解释观察到的TH水平降低，并可能导致污染物转运到发育中的胎儿中。
Persistent chemicals accumulate in the arctic environment due to their chemical reactivity and physicochemical properties and polychlorinated biphenyls (PCBs) are the most concentrated pollutant class in polar bears (Ursus maritimus). Metabolism of PCB and polybrominated biphenyl ether (PBDE) flame-retardants alter their toxicological properties and these metabolites are known to interfere with the binding of thyroid hormone (TH) to transthyretin (TTR) in rodents and humans. In polar bear plasma samples no binding of [(125)I]-T(4) to TTR was observed after incubation and PAGE separation. Incubation of the plasma samples with ((14)C)-4-OH-CB107, a compound with a higher binding affinity to TTR than the endogenous ligand T(4) resulted in competitive binding as proven by the appearance of a radio labeled TTR peak in the gel. Plasma incubation with T(4) up to 1 mM, a concentration that is not physiologically relevant anymore did not result in any visible competition. These results give evidence that the binding sites on TTR for T(4) in wild living polar bears are completely saturated. Such saturation of binding sites can explain observed lowered levels of THs and could lead to contaminant transport into the developing fetus.