Fukuoka Institute of Health and Environmental Sciences, 39 Mukaizano, Dazaifu, Fukuoka, 818-0135, Japan.
Kumamoto College, National Institute of Technology, 2627 Hirayamashin-Machi, Yatsushiro, Kumamoto, 866-8501, Japan.
Environ Sci Pollut Res Int. 2018 Jun;25(17):16455-16463. doi: 10.1007/s11356-017-9498-z. Epub 2017 Jun 21.
In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2',4,4',5,5'-hexaCB (CB153) concentration. The concentration ratios of tetra- and penta-chlorinated congeners in the blood of Yusho patients were significantly lower than those of controls. To examine the cytochrome P450 (CYP)-dependent metabolic potential of the 2,3',4,4'5-pentaCB (CB118), CB153, and 2,3,3',4,4'5-hexaCB (CB156) congeners, we conducted PCB-CYP (CYP1A1, CYP1A2, CYP2A6, and CYP2B6) docking simulation by in silico analysis. The docking models showed that human CYP1A1, CYP2A6, and CYP2B6 isozymes have the potential to metabolize CB118 and CB153. On the other hand, it was inferred that CB156 is difficult to be metabolized by these four CYP isozymes. These results indicate that CYP1 and CYP2 isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients.
在所谓的“油症”事件中，日本西部数千人因误食受多氯联苯（PCBs）和各种二恶英及类似二恶英化合物污染的米糠油而中毒。在这项研究中，我们调查了“油症”患者血液中 69 种 PCBs 同系物的积累模式，并将其与未暴露对照组进行了比较。这些血样是在 2004 年和 2005 年的体检中采集的。为了比较 PCB 同系物的模式，我们计算了每种同系物相对于 2,2',4,4',5,5'-六氯联苯（CB153）浓度的浓度比。“油症”患者血液中四氯和五氯代同系物的浓度比明显低于对照组。为了研究细胞色素 P450（CYP）依赖性代谢 2,3',4,4'5-五氯联苯（CB118）、CB153 和 2,3,3',4,4'5-六氯联苯（CB156）同系物的能力，我们通过计算机模拟进行了 PCB-CYP（CYP1A1、CYP1A2、CYP2A6 和 CYP2B6）对接模拟。对接模型表明，人 CYP1A1、CYP2A6 和 CYP2B6 同工酶具有代谢 CB118 和 CB153 的潜力。另一方面，据推断，这四种 CYP 同工酶难以代谢 CB156。这些结果表明，CYP1 和 CYP2 同工酶可能参与了“油症”患者血液中 PCB 同系物的特征性积累模式。
