Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma lipoprotein fractions
Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma lipoprotein fractions
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DOI：
10.1016/j.toxlet.2012.02.013
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发表时间：
2012-05-05
影响因子：
3.5
通讯作者：
Princen, Hans M. G.
中科院分区：
文献类型：
--
作者：
Butenhoff, John L.;Pieterman, Elsbeth;Princen, Hans M. G.
一些跨部门流行病学研究报告称，血清非高密度脂蛋白胆固醇浓度与血清全氟辛烷磺酸盐（PFOS）和全氟辛酸盐（PFOA）呈正相关。然而，在血清全氟辛烷磺酸和/或全氟辛酸浓度的三个数量级上，所报告的关联强度在确定-反应方面并不一致。根据毒理学/机制研究，这些积极的关联是出乎意料的，表明这些关联可能具有生物学基础，而不是因果关系基础。该研究检验了以下假设：全氟辛烷磺酸和全氟辛酸会分布到血清脂蛋白中，因此血清脂蛋白的增加会导致全氟辛烷磺酸和全氟辛酸血清浓度的相应增加。根据在使用超滤和LC-MS/MS方法进行的初步实验中观察到的全氟辛烷磺酸和全氟辛酸与生理盐水中分离的β-脂蛋白的结合（结合率分别为96%和40%），通过两种密度梯度方法研究了与人类供体血浆脂蛋白组分的结合情况。大多数全氟辛烷磺酸和全氟辛酸回收物都是在脂蛋白耗尽的血浆中发现的。血浆密度梯度分馏数据表明，最多9%的全氟辛烷磺酸分布在含脂蛋白的部分，而只有1%或更少的全氟辛酸分布在脂蛋白部分。这些数据不支持血浆脂蛋白组分在解释横断面流行病学研究中报告的不一致剂量-反应相关性方面的强有力作用。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Some cross-sectional epidemiological studies have reported positive associations of serum concentrations of non-high density lipoprotein cholesterol with serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). However, the strength of the reported associations is inconsistent for exposure-response across three orders of magnitude of serum PFOS and/or PFOA concentrations. These positive associations are unexpected based on toxicological/mechanistic studies, suggesting that the associations may have a biological, rather than a causal, basis. This study tested the hypothesis that PFOS and PFOA distribute into serum lipoprotein fractions such that increases in serum lipoproteins would result in corresponding increases in serum concentrations of PFOS and PFOA. Based on observed binding of PFOS and PFOA to isolated beta-lipoproteins in physiological saline (96% and 40% bound, respectively) in preliminary experiments using ultrafiltration and LC-MS/MS methods, binding to human donor plasma lipoprotein fractions was investigated by two density gradient methods. The majority of PFOS and PFOA recovered masses were found in lipoprotein-depleted plasma. Plasma density gradient fractionation data suggested that maximally 9% of PFOS distributes to lipoprotein-containing fractions, yet only 1% or less of PFOA is so distributed. These data do not support a strong role for plasma lipoprotein fractions in explaining the inconsistent dose-response associations reported in cross-sectional epidemiological studies. (C) 2012 Elsevier Ireland Ltd. All rights reserved.