Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences.
Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences.
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DOI：
10.1021/acs.est.2c00581
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发表时间：
2022-07-05
影响因子：
11.4
通讯作者：
Lehmler, Hans-Joachim
中科院分区：
文献类型：
--
作者：
Li, Xueshu;Hefti, Marco M.;Marek, Rachel F.;Hornbuckle, Keri C.;Wang, Kai;Lehmler, Hans-Joachim
关键词：
暴露于多氯联苯（PCB）及其羟基化代谢物（OH-PCB）与神经发育障碍有关。然而，PCBs和OH-PCBs在人脑中的分布尚未得到表征。本研究采用气相色谱-串联质谱法（GC-MS/MS）在新生儿（N = 7）和成人（N = 7）死后大脑样本的年龄，性别和大脑区域的特定分布的所有209多氯联苯。通过GC-MS/MS（作为甲基化衍生物）进行OH-PCB分析，并在一个样本子集中通过非目标液相色谱高分辨率质谱（Nt-LCMS）进行分析。共观察到14种高氯化多氯联苯同系物，检测频率> 50%。检测到六种低氯化多氯联苯，检测频率> 10%。在成年捐赠者的样本中观察到的氯化程度较高的多氯联苯含量高于年轻捐赠者。多氯联苯同系物配置文件从成人捐助者显示更多的相似性，在大脑区域和捐助者比年轻的捐助者。我们还评估了潜在的神经毒性的PCB残留物在人脑中的神经毒性当量（NEQ）的方法。根据多氯联苯同系物计算得出的中位CNOQ值，老年人比年轻人高出40倍。重要的是，氯化程度较低的多氯联苯对某些捐助者体内多氯联苯残留物的神经毒性潜力有相当大的贡献。通过GC-MS/MS和Nt-LCMS分析，首次在少数人脑样本中发现了OH-PCB，并且所有样本都含有4个或更少的氯。多氯联苯检测频率和水平是年龄和大脑区域的依赖性，而羟基化的多氯联苯在死后的人脑组织中检测频率低。
Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution of PCBs and OH-PCBs in the human brain has not been characterized. This study investigated the age-, sex-, and brain region-specific distribution of all 209 PCBs using gaschromatography–tandem mass spectrometry (GC–MS/MS) in neonatal (N = 7) and adult (N = 7) postmortem brain samples. OH-PCB analyses were performed by GC–MS/MS (as methylated derivatives) and, in a subset of samples, by nontarget liquid chromatography high-resolution mass spectrometry (Nt-LCMS). Fourteen higher chlorinated PCB congeners were observed with a detection frequency >50%. Six lower chlorinated PCBs were detected with a detection frequency >10%. Higher chlorinated PCBs were observed with higher levels in samples from adult versus younger donors. PCB congener profiles from adult donors showed more similarities across brain regions and donors than younger donors. We also assess the potential neurotoxicity of the PCB residues in the human brain with neurotoxic equivalency (NEQ) approaches. The median ΣNEQs, calculated for the PCB homologues, were 40-fold higher in older versus younger donors. Importantly, lower chlorinated PCBs made considerable contributions to the neurotoxic potential of PCB residues in some donors. OH-PCBs were identified for the first time in a small number of human brain samples by GC–MS/MS and Nt-LCMS analyses, and all contained four or fewer chlorine. PCB detection frequencies and levels are age- and brain region-dependent, whereas hydroxylated PCBs have low detection frequencies in postmortem human brain tissues.
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影响因子：
11.8
作者：
Milanowski, Bartlomiej;Lulek, Janina;Lehmler, Hans-Joachim;Kania-Korwel, Izabela
通讯作者：
Kania-Korwel, Izabela
DOI：
10.1007/s11356-018-2936-8
发表时间：
2018-10
期刊：
Environmental science and pollution research international
影响因子：
--
作者：
Abass K;Emelyanova A;Rautio A
通讯作者：
Rautio A
影响因子：
11.4
作者：
Feng W;Zheng J;Robin G;Dong Y;Ichikawa M;Inoue Y;Mori T;Nakano T;Pessah IN
通讯作者：
Pessah IN
影响因子：
11.4
作者：
Basu, Ilora;Arnold, Karen A.;Hites, Ronald A.
通讯作者：
Hites, Ronald A.
影响因子：
10.4
作者：
Dewailly, É;Mulvad, G;Hansen, JC
通讯作者：
Hansen, JC