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

1.在多氯联苯的羟化代谢方面，研究了大鼠、小鼠、仓鼠和豚鼠在多氯联苯混合物(Kanechlor500)作用下的物种差异。在仓鼠体内大量产生邻苯二酚多氯联苯(主要是di0H-CBH0)，而在大鼠和小鼠体内优先产生羟基化多氯联苯(主要是4-羟基-CB 107)和甲磺酰多氯联苯。豚鼠产生甲磺酰羟化的多氯联苯。所有二羟基多氯联苯都被发现来自2，5-或2，3，6-氯化多氯联苯。用大鼠、仓鼠和豚鼠的肝微粒体研究了PCB101的体外代谢。3-0H-，3‘-OH-，4’-OH-和3‘，4’-di0H-CB101分别由大鼠和豚鼠的肝微体形成。3‘-OH-CB101和4’-0H-CB101生成di0H-CB101的速率远高于CB101，苯巴比妥处理可加速生成di0H-CB101。结果表明，CB101向di0H-CB101的代谢主要是由CYP2B酶催化的，相对于CB101.3，该酶更倾向于4‘-0H-和3’-OH。人血中残留的羟基多氯联苯为4-0H-CB107、4-0H-CB146和4-0H-CB187。为了进一步研究二氢多氯联苯在人体内的负荷，采用电子捕获负电离-气相色谱-质谱仪(ECNI-GC)对福冈居民的血液样品进行了分析。结果在人体血液中检测到1种二氢二氯联苯，鉴定为4，5-(OH)_2-2，3，6，2‘，4’，5‘-六氯联苯(di0H-CB149)。羟基多氯联苯，包括儿茶酚多氯联苯，可能会降低人体内的甲状腺激素水平，因此需要进行进一步的监测和毒理学意义的研究。

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.