Species difference in hydroxylation of polychlorinated biphenyls and exposure of metabolites in human blood.

多氯联苯羟基化和人体血液中代谢物暴露的物种差异。

• 批准号: 16590101
• 负责人: HARAGUCHI Koichi
• 金额: $ 2.3万
• 依托单位: Daiichi College of Pharmaceutical Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590101/
• 关键词: PCB; hydroxylated metabolites; human; blood; species difference; catechol; カテコール代謝物; Gunnラット; ハムスター; GC-MS; UGT活性

1. In the hydroxylation metabolism of polychlorinated biphenyls (PCBs), species differences were studied in rats, mice, hamsters and guinea pigs dosed with PCB mixture (Kanechlor 500). Catechol PCBs (mainly di0H-CBH0) were highly produced in hamsters, while hydroxylated PCBs (mainly 4-OH-CB 107) and methylsulfonyl PCBs were preferably produced in rats and mice. Guinea pigs produced methylsulfonyl-hydroxylated PCBs. All diOH-PCBs were found to be derived from 2,5-or 2,3,6-chlorinated PCBs.2. The in vitro metabolism of PCB 101 was studied using liver microsomes of rats, hamsters and guinea pigs.3-0H-, 3'-OH-, 4'-OH-and 3',4'-di0H-CB101 were formed by liver microsomes of rats and guinea pigs. The formation of di0H-CB101 from 3'-OH-and 4'-0H-CB101 proceeded at much higher rate than that from CB101 and was accelerated by phenobarbital-treatment. The result indicated that the metabolism of CB 101 to di0H-CB101 is principally catalyzed by CYP2B enzymes, which prefer 4'-0H-and 3'-OH to CB101.3. Hydroxyl Ted PCBs retained in human blood were found to be 4-0H-CB107, 4-0H-CB146 and 4-0H-CB187.In order to further investigate the body burden of di0H-PCBs in human, blood samples from Fukuoka residents were analyzed by electron capture negative ionization-gas chromatography-mass spectrometry (ECNI-GC), using 18 synthesized references (veratrolic PCBs) for catechol metabolites. As a result, one di0H-PCB was detected in human blood, and identified as 4,5-(OH)_2-2,3,6,2',4',5'-hexaCB (di0H-CB149).Further monitoring and toxicological significance of hydroxylated PCBs including catecholic PCBs should be performed, since these metabolites may decrease the thyroxine levels in human body.

1. 在多氯联苯（PCB）羟基化代谢中，研究了大鼠、小鼠、仓鼠和豚鼠在多氯联苯混合物（Kanechlor 500）剂量下的物种差异。在仓鼠体内大量产生儿茶酚类多氯联苯（主要是di0H-CBH0），而在大鼠和小鼠体内主要产生羟基化多氯联苯（主要是4- oh - cb107）和甲基磺酰多氯联苯。豚鼠产生甲基磺酰羟基化多氯联苯。所有的二恶英多氯联苯均来源于2,5或2,3,6氯化多氯联苯。用大鼠、仓鼠和豚鼠肝微粒体研究了PCB 101的体外代谢。3- 0h -, 3'- oh -, 4'- oh -和3',4'- di0h - cb101由大鼠和豚鼠肝微粒体形成。3′- oh和4′-0H-CB101生成di0H-CB101的速率远高于CB101，且苯巴比妥处理可加速di0H-CB101的生成。结果表明，cb101向di0H-CB101的代谢主要由CYP2B酶催化，CYP2B酶对CB101.3偏爱4′- 0h和3′-OH。人体血液中保留的羟基泰德多氯联苯分别为4-0H-CB107、4-0H-CB146和4-0H-CB187。为了进一步了解人体对二氢多氯联苯的负荷，采用电子捕获负电离-气相色谱-质谱法（ECNI-GC）对福冈居民血液样本进行了儿茶酚代谢物的分析，采用18种合成参考物（veratrolic PCBs）。结果，在人血中检测到一种di0H-PCB，鉴定为4,5-(OH)_2-2,3,6,2',4',5'- hexacb （di0H-CB149）。羟基化多氯联苯（包括儿茶酚类多氯联苯）的代谢产物可能降低人体内甲状腺素水平，因此应进一步监测这些代谢产物的毒理学意义。

项目成果

2,2',3,4',5,5',6-七塩素化ビフェニル(CB187)の主代謝物の合成

2,2,3,4,5,5,6-七氯联苯(CB187)主要代谢物的合成

• 发表时间: 2006
• 期刊: 中村学園大学 研究紀要 38
• 作者: Yamaguchi Y;Yamada K;Yoshikawa N;Nakamura K;Haginaka J;Kunitomo M.;T.Funahashi et al.;M.Yotoriyama et al.;T.Funahashi et al.;K.Watanabe et al.;T.Matsunaga et al.;T.Funahashi et al.;Yasuo Seto;太田千穂
• 通讯作者: 太田千穂

Species differences in tissue distribution of catechol and methylsulphonyl metabolites of polychlorinated biphenyls in rats, mice, hamsters and guinea pigs.

大鼠、小鼠、仓鼠和豚鼠体内儿茶酚和多氯联苯甲磺酰代谢物的组织分布存在物种差异。

• 发表时间: 2005
• 期刊: Xenobiotica (in press)
• 作者: K.Haraguchi;Y.Kato;N.Koga;M.Degawa
• 通讯作者: M.Degawa

Metabolism of polychlorinated biphenyls by Gunn rats: Identification and serum retention of catechol metabolites

• DOI: 10.1021/tx0498096
• 发表时间: 2004-12-01
• 期刊: CHEMICAL RESEARCH IN TOXICOLOGY
• 影响因子: 4.1
• 作者: Haraguchi, K;Kato, Y;Degawa, M
• 通讯作者: Degawa, M

Metabolism of 2, 3', 4, 4', 5-penta-chlorobiphenyl in guinea pig microsomes.

2, 3, 4, 4, 5-五氯联苯在豚鼠微粒体中的代谢。

• 发表时间: 2005
• 期刊: Fukuoka Acta Medica 96
• 作者: Chizuko Miyake-Nakayama;Sachiyo Masujima;Hisayoshi ikatsu;Shin-ich Miyoshi;Sumio Shinoda;Choji Fukuhara;Chiho Ohta
• 通讯作者: Chiho Ohta

In vitro metabolism of 2,2′,3,4′,5,5′,6-heptachlorobiphenyl (CB187) by liver microsomes from rats, hamsters and guinea pigs

• DOI: 10.1080/00498250500087507
• 发表时间: 2005-04-01
• 期刊: XENOBIOTICA
• 影响因子: 1.8
• 作者: Ohta, C;Haraguchi, K;Koga, N
• 通讯作者: Koga, N