McGraw Joseph E, Waller Donald P
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Biochem Biophys Res Commun. 2006 May 26;344(1):129-33. doi: 10.1016/j.bbrc.2006.03.122. Epub 2006 Mar 29.
Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2',4',5,5') is a common, persistent non-coplanar PCB congener found in the ambient environment but information related to its metabolism in humans is lacking. Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP 2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in hamsters was also reported. To specifically identify the human CYP 450 isoforms responsible for PCB 101 metabolism, we compared human microsome metabolism to metabolism using several specific recombinant human CYP isoforms. These data characterized selective and extensive metabolism by human CYP 2A6. The product formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2',4',5,5') and was the only major metabolite observed in the recombinant and human microsome investigation. This is important information for predicting human specific toxicokinetics of PCBs.
多氯联苯国际纯粹与应用化学联合会编号#101 - 多氯联苯101（氯化模式 - 2,2',4',5,5'）是在环境中常见的、持久性的非共面多氯联苯同系物，但缺乏有关其在人体内代谢的信息。先前的研究表明，多氯联苯101在哺乳动物体内通过细胞色素P450 2B和3A家族酶快速代谢。最近，也有报道称仓鼠体内通过细胞色素P450 2A家族同工型进行多氯联苯代谢。为了具体确定负责多氯联苯101代谢的人类细胞色素P450同工型，我们将人微粒体代谢与使用几种特定重组人细胞色素P450同工型的代谢进行了比较。这些数据表明人细胞色素P450 2A6具有选择性和广泛的代谢作用。形成的产物是4 - 羟基 - 多氯联苯101代谢物（4 - 羟基 - 2,2',4',5,5'），并且是在重组和人微粒体研究中观察到的唯一主要代谢物。这对于预测多氯联苯在人体内的特定毒代动力学是重要信息。
