The role of 3-methylsulfony (3-MeSOィイD22ィエD2) metabolites in the induction of hepatic microsomal drug-metabolizing enzymes by PCB congeners, and the toxicological effects of the MeSOィイD22ィエD2 metabolites of PCB congeners

当前研究的目标是通过多氯联苯（PCB） congeners改变的Hepatic microsomal drug-metabolization enzyme系统的作用来澄清3-methylsulfonyl（3-MeSO）的作用。此外，我们还研究了3-和4-MeSO中的生物活性和毒性效应的D22中的D2代谢物。我们合成了7 - 3-MeSO-D22-D2和2-MeSO-D22-D2多氯联苯聚合物的元细胞（有报告称仍在人类牛奶、下游和注射组织以及几种哺乳动物物种中）及其两个结构相似的3-MeSO-D22-PCBs。The results of present study show that the structure-CYP2B1/2 induction relationship exists for the 3-MeSOイD22エD2 derivatives studied.2。结果显示3-MeSO-D2-2 -2，2'，4'，5，5'-五氯苯基（3-MeSO-D2-2 -2，2'，4'，5，5'-五氯苯基）是一种潜在的苯巴比妥（PB）--肝炎药物代谢酶在两种男性和女性老鼠， a ... More nd that there is no sex difference in the induction of the drug-metabolization enzyme activities by treatment with 3-MeSOイD2 - 2イエD2-2，2'，4'，5，5'-pentaCB。The 4-MeSOイイD22エD2 isomer had little effect in both male and female rats.3.结果表明，2，2'，4，5，5'-五烯CB对某些药物代谢酶和δ-氨基烯烃酸合成酶的定义并不对2，2 '，4，5，5'-五烯CB本身起作用，但对它3-甲基磺酰甲烷，3-MeSO-D2 -2 -2，2'，4'，5，5'-五烯CB.4。该结果显示了3-和4-MeSO-D22-D2元器件测试的PCB聚合物的抑制间隙接头间通信与其父元器件相同的潜力。由于细胞通信受到抑制，在多次肿瘤启动子的治疗后经常受到观察，结果建议代谢物也可能作为肿瘤启动子产生作用。该结果显示了已经测试的九个3-和4-MeSO-D22-D2元的四、五、六进制CBs减少老鼠中的激素水平，并建议这些元可以作为内分泌干扰器的行为。The results indicate that increase in the hepatic thyroxine （T-D24-D2 glucuronidation after the administration of the seven 3-MeSO-D2 - 2-PCBs and 4-MeSO-D2-2 -2，2'，4'，5，5'-pentaCB possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum T-D24-D2 levels）。Less（低）

The purpose of the present study was to clarify the role that 3-methylsulfonyl (3-MeSOィイD22ィエD2) metabolites play in altering the hepatic microsomal drug-metabolizing enzyme system by polychlorinated biphenyl (PCB) congeners. Additionally we have investigated the biological activities and toxicological effects of the 3- and 4-MeSOィイD22ィエD2 metabolites of PCB congeners. We synthesized eleven 3-MeSOィイD22ィエD2 and two 4-MeSOィイD22ィエD2 metabolites of PCB congeners (which were reported to remain in human milk, liver and adipose tissue and the tissues of several mammalian species) and their two structurally similar 3-MeSOィイD22ィエD2-PCBs.1. The results of present study show that the structure-CYP2B1/2 induction relationship exists for the 3-MeSOィイD22ィエD2 derivatives studied.2. The results show that 3-MeSOィイD22ィエD2-2,2',4',5,5'-pentachlorobiphenyl (3-MeSOィイD22ィエD2-2,2',4',5,5'-pentaCB) is a potent phenobarbital (PB)-type inducer of hepatic drug-metabolizing enzymes in both male and female rats, a … More nd that there is no sex difference in the induction of the drug-metabolizing enzyme activities by treatment with 3-MeSOィイD22ィエD2-2,2',4',5,5'-pentaCB. The 4-MeSOィイD22ィエD2 isomer had little effect in both male and female rats.3. The results provide the evidence that the induction of some drug-metabolizing enzymes and δ-aminolevulinic acid synthetase by 2,2',4,5,5'-pentaCB is due not to the action of 2,2',4,5,5'-pentaCB itself but to its 3-methylsulfonyl metabolite, 3-MeSOィイD22ィエD2-2,2',4',5,5'-pentaCB.4. The results show that 3- and 4-MeSOィイD22ィエD2 metabolites of the PCB congeners tested inhibit gap junction intercellular communication at about the same potency as their parental compounds. Since inhibition of cell communication is often observed after treatment with many tumor promoters, the results suggest that the metabolites may also act as tumor promoters.5. The results show that the nine tested 3- and 4-MeSOィイD22ィエD2 metabolites of tetra-, penta- and hexaCBs reduce throid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.6. The results indicate that increase in the hepatic thyroxine (TィイD24ィエD2 glucuronidation after the administration of the seven 3-MeSOィイD22ィエD2-PCBs and 4-MeSOィイD22ィエD2-2,2',4',5,5'-pentaCB possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum TィイD24ィエD2 levels. Less