Correlations between polychlorinated biphenyl immunotoxicity, the aromatic hydrocarbon locus, and liver microsomal enzyme induction in C57BL/6 and DBA/2 mice.
Correlations between polychlorinated biphenyl immunotoxicity, the aromatic hydrocarbon locus, and liver microsomal enzyme induction in C57BL/6 and DBA/2 mice.
复制标题
C57BL/6 和 DBA/2 小鼠中多氯联苯免疫毒性、芳香烃位点和肝微粒体酶诱导之间的相关性。
DOI：
10.1016/0041-008x(84)90086-3
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发表时间：
1984
影响因子：
3.8
通讯作者：
Kaminsky,LS
中科院分区：
文献类型：
--
作者：
Silkworth,JB;Antrim,L;Kaminsky,LS
多氯联苯 (PCB) 对小鼠抗体反应的抑制取决于 PCB 分子的平面性和芳香烃 (Ah) 受体的表达。在这项研究中，假设这种形式的免疫毒性是 Ah 基因复合物激活的结果，并且作为 Ah 受体配体的其他化合物也将具有免疫毒性。在用绵羊免疫前 2 天，将 2,2',4,4'-四氯联苯 (TCB)、2,3,3',4,4',5-六氯联苯 (HCB)、苯巴比妥 (PB) 或 β-萘黄酮 (BNF) 腹膜内给予 C57BL 6 (B6, AhbAhb) 或 DBA 2 (D2, AhdAhd) 小鼠红细胞。第 5 天评估器官重量、组织病理学、血凝抗体滴度和脾直接抗体空斑形成细胞 (PFC) 反应。测量这些化合物以及 2,2',5,5'-TCB 和 3,3',4,4'-TCB 诱导的肝芳烃羟化酶 (AHH)，作为 Ah 受体结合和随后甲基胆蒽型诱导剂激活 Ah 基因复合物的指标，同时测量氨基比林 N-去甲基酶 (APND) 作为 PB 型诱导的指标。 2,2',4,4'-TCB 和 PB 对任一菌株的免疫参数均无影响，但诱导两种菌株的 APND 活性。 2,2',5,5'-TCB 轻微诱导 B6 小鼠的 APND 活性。 2,3,3',4,4',5-HCB 导致每个脾脏 PFC 抑制 70%，降低血清抗体滴度，升高细胞色素 P-450 水平 (193%)，在 B6 小鼠中诱导 APND (165%) 和 AHH (217%) 活性，但在 D2 小鼠中仅诱导 APND (156%) 活性。 3,3',4,4'-TCB 升高 B6 小鼠中的细胞色素 P-450 水平 (210%)，并诱导 APND (129%) 和 AHH (321%) 活性，但仅增加 D2 小鼠中的 APND 活性 (115%)。 BNF 升高细胞色素 P-450 (144%)，导致每个脾脏 PFC 抑制 49%，并诱导 APND (156%) 和 AHH (248%) 活性，但仅限于 B6 小鼠。这些结果支持这样的假设：卤代和多环芳烃引起的免疫毒性是 Ah 基因复合物激活的结果，并表明这种毒性作用可以由任何 Ah 受体配体引发。
The suppression of the antibody response by polychlorinated biphenyls (PCB) in mice is dependent on the planarity of the PCB molecule and on the expression of the aromatic hydrocarbon (Ah) receptor. In this study, the hypothesis that this form of immunotoxicity is a consequence of the activation of the Ah gene complex and that other compounds which are Ah receptor ligands would also be immunotoxic was tested. 2,2′,4,4′-Tetrachlorobiphenyl (TCB), 2,3,3′,4,4′,5-hexachlorobiphenyl (HCB), phenobarbital (PB), or β-naphthoflavone (BNF) was given ip to either C57BL 6 (B6, AhbAhb) or DBA 2 (D2, AhdAhd) mice 2 days before immunization with sheep erythrocytes. Organ weights, histopathology, hemagglutinating antibody titers, and the splenic direct antibody plaque-forming cell (PFC) response were evaluated on Day 5. Hepatic aryl hydrocarbon hydroxylase (AHH) induction by these compounds and by 2,2′,5,5′-TCB and 3,3′,4,4′-TCB was measured as an indicator of Ah receptor binding and subsequent activation of the Ah gene complex by methylcholanthrene-type inducers, while aminopyrine N-demethylase (APND) was measured as an indicator of PB-type induction. 2,2′,4,4′-TCB and PB had no effects on the immune parameters of either strain but induced APND activity in both strains. 2,2′,5,5′-TCB slightly induced APND activity in B6 mice. 2,3,3′,4,4′,5-HCB caused a 70% suppression of PFC per spleen, decreased the serum antibody titer, elevated cytochrome P-450 levels (193%), induced both APND (165%) and AHH (217%) activity in B6 mice, but it induced only APND (156%) activity in D2 mice. 3,3′,4,4′-TCB elevated cytochrome P-450 levels (210%) and induced both APND (129%) and AHH (321%) activities in B6 mice but only increased APND activities (115%) in D2 mice. BNF elevated cytochrome P-450 (144%), caused a 49% suppression in PFC per spleen, and induced both APND (156%) and AHH (248%) activities but only in B6 mice. These results support the hypothesis that the immunotoxicity caused by halogenated and polycyclic aromatic hydrocarbons is a consequence of activation of the Ah gene complex and suggests that this toxic effect can be initiated by any Ah receptor ligand.