Voie O A, Fonnum F
Norwegian Defence Research Establishment, Division for Environmental Toxicology, P.O. Box 25, 2027 Kjeller, Norway.
Arch Toxicol. 2000 Jan;73(10-11):588-93. doi: 10.1007/s002040050012.
In this paper the effect of polychlorinated biphenyls (PCBs) on the production of reactive oxygen species (ROS) in rat synaptosomes is elucidated. The effect of methylmercury (MeHg) on rat synaptosomes was included as a positive control since several studies have investigated the ability of this substance to produce ROS. The exposure of the synaptosomes to the congener 2,2-dichlorobiphenyl (2, 2'-DCB; 12.5 microM) produced a linear increase in the formation of 2',7'-dichlorofluorescein (DCF) as a measure for the production of ROS. The congeners 2,2'-DCB (12.5 microM) and 3,3'-DCB (12.5 microM) stimulated, as expression of ROS production, a significant increase in DCF formation formation compared to the control. The congeners 2-chlorobiphenyl (2-CB) and 2,2',6-trichlorobiphenyl (2,2,6'-TCB) were active at 50 microM, whereas 2,2',4,4',5,5'-hexachlorobiphenyl (2,2',4,4',5,5'-HCB), 4,4'-DCB and 2,2',6,6'-tetrachlorobiphenyl (2, 2',6,6'-TeCB) were not active at this concentration. The increased formation of ROS in response to 2,2'-DCB and MeHg in the synaptosomes was dependent on extracellular Ca(2+). A phospholipase C inhibitor, U73122, was shown to significantly decrease the ROS formation induced by 2,2'-DCB, but did not reduce the ROS formation induced by MeHg. Ethanol (1%), a phospholipase D modulator, reduced the ROS formation induced by MeHg and by 2,2'-DCB by 33 and 52%, respectively. Wortmannin (25 nM), an inhibitor of phosphatidylinositol 3-kinase, completely inhibited the ROS formation induced by MeHg and 2,2'-DCB. It appears that the ROS-stimulating PCBs are the same congeners found to be neuroactive in other types of study. Phospholipase C and D and phosphatidylinositol 3-kinase seem to be involved in the intracellular signalling system that leads to ROS formation during PCB exposure.
本文阐述了多氯联苯（PCBs）对大鼠突触体中活性氧（ROS）生成的影响。甲基汞（MeHg）对大鼠突触体的影响作为阳性对照，因为已有多项研究探讨了该物质产生活性氧的能力。将突触体暴露于同系物2,2 - 二氯联苯（2,2'-DCB；12.5微摩尔）会使2',7'-二氯荧光素（DCF）的生成呈线性增加，以此作为活性氧生成的指标。同系物2,2'-DCB（12.5微摩尔）和3,3'-DCB（12.5微摩尔）作为活性氧生成的表现形式，与对照组相比，显著刺激了DCF生成的增加。同系物2 - 氯联苯（2 - CB）和2,2',6 - 三氯联苯（2,2,6'-TCB）在50微摩尔时具有活性，而2,2',4,4',5,5'-六氯联苯（2,2',4,4',5,5'-HCB）、4,4'-DCB和2,2',6,6'-四氯联苯（2,2',6,6'-TeCB）在此浓度下无活性。突触体中因2,2'-DCB和MeHg导致的活性氧生成增加依赖于细胞外钙离子（Ca(2+)）。一种磷脂酶C抑制剂U73122被证明可显著降低2,2'-DCB诱导的活性氧生成，但不能降低MeHg诱导的活性氧生成。乙醇（1%）作为一种磷脂酶D调节剂，分别使MeHg和2,2'-DCB诱导的活性氧生成降低了33%和52%。渥曼青霉素（25纳摩尔）作为磷脂酰肌醇3 - 激酶的抑制剂，完全抑制了MeHg和2,2'-DCB诱导的活性氧生成。似乎刺激活性氧生成的多氯联苯同系物与在其他类型研究中发现具有神经活性的同系物相同。磷脂酶C、D和磷脂酰肌醇3 - 激酶似乎参与了多氯联苯暴露期间导致活性氧生成的细胞内信号系统。
