Osaka Institute of Public Health, 1-3-69 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan.
Research Center for Environment Preservation, Osaka University, 2-4 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Environ Sci Pollut Res Int. 2018 Jun;25(17):16420-16426. doi: 10.1007/s11356-017-0434-z. Epub 2017 Oct 17.
2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183) possess axial chirality and form the aS and aR enantiomers. The enantiomers of these congeners have been reported to accumulate in the human body enantioselectively via unknown mechanisms. In this study, we determined the cytochrome P450 (CYP) monooxygenase responsible for the enantioselective oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase. We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95 enantioselectively; however, it did not oxidize PCB 183. The enantiomer composition was elevated from 0.5 (racemate) to 0.54. In addition, following incubation with CYP2A6, the enantiomer fraction (EF) of PCB 95 demonstrated a time-dependent increase.
2,2',3,5',6-五氯联苯（PCB95）和 2,2',3,4,4',5',6-七氯联苯（PCB183）具有轴向手性，形成 aS 和 aR 对映异构体。这些同系物的对映异构体已被报道通过未知机制在人体中选择性地积累。在这项研究中，我们使用重组人细胞色素 P450（CYP）单加氧酶来确定负责 PCB95 和 PCB183 对映选择性氧化的 CYP 单加氧酶。我们评估了 13 种 CYP 单加氧酶，即 CYP1A1、CYP1A2、CYP1B1、CYP2A6、CYP2B6、CYP2C8、CYP2C19、CYP2E1、CYP2J2、CYP3A4、CYP3A5、CYP4F2 和芳香酶（CYP19），并揭示 CYP2A6 优先对 aS-PCB95 进行对映选择性氧化；然而，它不能氧化 PCB183。对映异构体的组成从 0.5（外消旋体）升高到 0.54。此外，在用 CYP2A6 孵育后，PCB95 的对映体分数（EF）表现出时间依赖性增加。
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