Accumulation properties of polychlorinated biphenyl congeners in Yusho patients and prediction of their cytochrome P450-dependent metabolism by in silico analysis

Shusaku Hirakawa, Takashi Miyawaki, Tsuguhide Hori, Jumboku Kajiwara, Susumu Katsuki, Masashi Hirano, Yuka Yoshinouchi, Hisato Iwata, Chikage Mitoma, Masutaka Furue

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)16455-16463
ページ数9
ジャーナルEnvironmental Science and Pollution Research
25
17
DOI
出版ステータス出版済み - 6 1 2018

All Science Journal Classification (ASJC) codes

  • Environmental Chemistry
  • Pollution
  • Health, Toxicology and Mutagenesis

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