Polychlorinated biphenyl immunotoxicity: dependence on isomer planarity and the Ah gene complex.
Polychlorinated biphenyl immunotoxicity: dependence on isomer planarity and the Ah gene complex.
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多氯联苯免疫毒性：依赖于异构体平面性和 Ah 基因复合物。
DOI：
10.1016/0041-008x(82)90368-4
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发表时间：
1982
影响因子：
3.8
通讯作者：
Grabstein,EM
中科院分区：
文献类型：
--
作者：
Silkworth,JB;Grabstein,EM
某些卤代芳烃的性质，如胞质受体结合，芳烃羟化酶和细胞色素P-450诱导，和胸腺萎缩，在小鼠中与Ah（芳烃）基因复合物分离。本研究测试的假设，多氯联苯（PCB）在小鼠中的免疫毒性也与Ah基因复合物分离，并依赖于PCB分子的平面性。雄性C 57 BL 6（Ah+）和DBA 2（Ah-）小鼠在绵羊红细胞（SRBC）静脉免疫前2天和免疫后2天，以0、10或100 mg/kg的玉米油溶液ip给予平面3，4，3 ′，4 ′-四氯联苯（TCB）或非平面2，5，2 ′，5 ′-TCB。免疫后5天，通过Jerne空斑试验评价一次抗体应答。3，4，3 ′，4 ′-TCB使每106个脾细胞中的抗SRBC抗体形成细胞数和每个脾中的抗SRBC抗体形成细胞数分别比对照值降低79%和90%。该异构体还引起胸腺萎缩、肝肿大、肝小叶中心肥大和广泛的肝脂肪浸润;体重和相对脾/体重降低;并诱导细胞色素P-450。在C57 BL 6小鼠中观察到这些效应，而在DBA 2小鼠中未观察到. 2，5，2 ′，5 ′-TCB在两种菌株中均未产生任何这些效应。这些结果与我们的假设是一致的，并表明，PCB免疫毒性介导通过遗传控制的胞质受体存在于C 57 BL 6，但不是在DBA 2小鼠和PCB异构体的免疫毒性潜力是依赖于它们的构象平面性。
Properties of certain halogenated aromatic hydrocarbons, such as cytosolic receptor binding, aryl hydrocarbon hydroxylase and cytochrome P-450 induction, and thymic atrophy, segregate with the Ah (aromatic hydrocarbon) gene complex in mice. This study tested the hypothesis that polychlorinated biphenyl (PCB) immunotoxicity in mice also segregates with the Ah gene complex and is dependent on the planarity of the PCB molecule. Male C 57 BL 6 (Ah+) and DBA 2 (Ah−) mice were administered planar 3,4,3′,4′-tetrachlorobiphenyl (TCB) or nonplanar 2,5,2′,5′-TCB at doses of either 0, 10, or 100 mg/kg ip in corn oil 2 days prior to and 2 days after iv immunization with sheep erythrocytes (SRBC). Five days after immunization the primary antibody response was evaluated by the Jerne plaque assay. 3,4,3′,4′-TCB significantly decreased the number of anti-SRBC antibody-forming cells per 106spleen cells and per spleen by 79 and 90%, respectively, from control values. This isomer also caused thymic atrphy, hepatomegaly, hepatic centrilobular hypertrophy, and extensive hepatic fatty infiltration; decreased body and relative spleen/body weights; and induced cytochrome P-450. These effects were observed in C 57 BL 6 but not in DBA 2 mice. 2,5,2′,5′-TCB did not produce any of these effects in either strain. These results are consistent with our hypothesis and suggest that PCB immunotoxicity is mediated through a genetically controlled cytosolic receptor present in C 57 BL 6 but not in DBA 2 mice and that the immunotoxic potential of PCB isomers is dependent on their conformational planarity.
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