Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254
Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254
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DOI：
10.1006/taap.1998.8534
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发表时间：
1998-12-01
影响因子：
3.8
通讯作者：
Tilson, HA
中科院分区：
文献类型：
--
作者：
Kodavanti, PRS;Ward, TR;Tilson, HA
我们以前在体外研究与分离的细胞器和原代神经元细胞培养物发现，细胞内的信号转导可以受到干扰的一些noncoplanar PCBs在暴露水平小于或等于10 μ M。然而，尚不清楚在体内脑中是否可达到这样的浓度。此外，对接触商用多氯联苯混合物的动物的组织中多氯联苯的同系物分布和累积量的模式也没有进行充分的研究。在本研究中，我们对口服Aroclor 1254的成年雄性Long-Evans大鼠的不同脑区、肝脏、血液和脂肪中的PCB同源物进行了特异性分析（0或30 mg/kg/天;每天一次，5天/周，持续4周）。最后一次给药后24小时，将大鼠安乐死，取出脑并解剖以获得小脑，额叶皮质，和纹状体。同时采集肝脏、血液和脂肪样本。多氯联苯的同源特异性分析采用高分辨率气相色谱-电子捕获检测器。对照组大鼠脑区的多氯联苯浓度低于百万分之0.02，而处理组动物体内的多氯联苯同系物总量则累积到更高的水平。额叶皮质、小脑和纹状体中的总水平分别为15.1 +/- 0.3、13.1 +/- 1.7和8.2 +/- 2.6 ppm。多氯联苯在脂肪，肝脏和血液中的水平分别为0.041，0.002和0.001 ppm的对照大鼠和552，38.3和1.6 ppm的治疗大鼠，分别。除了组织之间的差异总吸收，有差异积累的多氯联苯相对于氯的数量。在所有组织中，较轻度氯化（四氯化物和五氯化物）同系物的累积量低于其在母体多氯联苯1254混合物中的相应比例。另一方面，高度氯化的（六氯至九氯）同源物的累积量超过了在多氯联苯1254混合物中发现的这些同源物的比例。这种向高氯化同系物积累的转变在大脑中似乎比肝脏和脂肪中更明显。主要同系物在不同的大脑区域、血液、肝脏和脂肪中检测到的PCB（占PCB总量的5-32%）分别为：2，3，3 '，4'，5，6-（第163号）+2，2 '，3，4，4'，5-（第138号）（共洗脱）; 2，2 '，4，4'，5，5 '-（第153号）+2，2 '，3，3'，4，6 '-（第132号）（共洗脱）; 2，3，3 '，4，4'，5-（编号156）+2，2 '，3，3'，4，4 '，6-（编号171）（共洗脱）; 2，3'，4，4 '，5-（编号118）; 2，2'，4，4 '，5-（编号99）;和2，3，3'，4，4 '-（编号105）。这些同源物加起来约占大脑中PCB总负荷的三分之二。所有这些主要同系物都是邻位取代的，因此在性质上是不共面的。在大脑中积累的总PCB浓度高达50 μ M（基于Aroclor 1254的平均分子量为326.4），在这些浓度下，细胞内第二信使在体外神经元培养物和脑匀浆制剂中受到显着影响。这些结果表明，在重复暴露后，在体内脑中可达到改变体外Ca 2+处置和第二信使系统的浓度，（C）1998 Academic Press。
Our previous in vitro studies with both isolated organelles and primary neuronal cell cultures found that intracellular signal transduction can be perturbed by some noncoplanar PCBs at exposure levels of less than or equal to 10 mu M. However, it is not clear whether such concentrations are achievable in brain in vivo. Also, the pattern of congener disposition and quantities of the PCB accumulation in tissues of animals exposed to commercial PCB mixtures is not well studied. In the present study, we have conducted PCB congener-specific analysis in different brain regions, liver, blood, and fat of adult male Long-Evans rats dosed orally with Aroclor 1254 (0 or 30 mg/kg/day; once per day, 5 days/week for 4 weeks) in corn on. Twenty-four hours after the last dose, rats were euthanized, and the brains were removed and dissected to obtain cerebellum, frontal cortex, and striatum. Liver, blood, and fat samples were also collected at the same time. Congener-specific analysis of PCBs was performed by high-resolution gas chromatography with electron capture detection. While PCB concentrations in control rat brain regions were less than 0.02 ppm, total PCB congeners in treated animals accumulated to much higher levels. Total levels in the frontal cortex, cerebellum, and striatum were 15.1 +/- 0.3, 13.1 +/- 1.7, and 8.2 +/- 2.6 ppm, respectively. The levels of PCBs in the fat, liver, and blood were 0.041, 0.002, and 0.001 ppm in control rats and 552, 38.3, and 1.6 ppm in treated rats, respectively. In addition to the differential total uptake between tissues, there was differential accumulation of PCBs with respect to the number of chlorines. In all the tissues, the more lightly chlorinated (tetra- and penta-) congeners accumulated less than their respective proportions in the parent Aroclor 1254 mixture. On the other hand, heavily chlorinated (hexa- to nona-) congeners accumulated more than the proportion of these congeners found in Aroclor 1254 mixture. This shift toward accumulation of heavily chlorinated congeners seems to be more pronounced in the brain than liver and fat. Predominant congeners (5-32% of total PCBs) detected in different brain regions, blood, liver, and fat are: 2,3,3',4',5,6- (no. 163)+ 2,2',3,4,4',5- (no. 138)(coeluted); 2,2',4,4',5,5'- (no. 153)+ 2,2',3,3',4,6'- (no. 132) (coeluted); 2,3,3',4,4',5- (no. 156) + 2,2',3,3',4,4',6- (no. 171) (coeluted); 2,3',4,4',5- (no. 118); 2,2',4,4',5-(no. 99); and 2,3,3',4,4'- (no. 105). These congeners together accounted for about two thirds of the total PCB load in brain. All these predominant congeners are ortho-substituted and therefore are noncoplanar in nature. The total PCB concentrations accumulated in brain were as high as 50 mu M (based on average molecular weight of 326.4 for Aroclor 1254) and, at these concentrations, intracellular second messengers were significantly affected in neuronal cultures and brain homogenate preparations in vitro. These results indicate that concentrations that altered Ca2+ disposition and second messenger systems in vitro are achievable in brain in vivo following repeated exposure, (C) 1998 Academic Press.