Rifkind A B, Firpo A, Alonso D R
Toxicol Appl Pharmacol. 1984 Feb;72(2):343-54. doi: 10.1016/0041-008x(84)90319-3.
Hepatic histologic changes and induction of mixed function oxidases were examined and compared after administration to the chick embryo of four highly purified polychlorinated biphenyl (PCB) congeners: 3,4,3',4'-tetrachlorobiphenyl (TCB) and 3,4,5,3',4',5'-, 2,4,5,2',4',5'-, and 2,3,6,2',3',6'-hexachlorobiphenyls (HCBs). The major histopathologic change was hepatocyte swelling as evidenced by sinusoidal narrowing. It was observed within 24 hr after PCB administration at doses as low as 5 nmol/egg for 3,4,3',4'-TCB and 3,4,5,3',4',5'-HCB and only at doses of 5000 nmol/egg and higher for 2,4,5,2',4',5'-HCB. 2,3,6,2',3',6'-HCB was inactive. The histopathologic change was predominantly perivascular in distribution. It was accompanied by increased hepatic water content. Occasional hepatocytes showed nuclear pyknosis and cytoplasmic eosinophilia, but there was little histologic evidence of frank necrosis and no biochemical evidence, since serum glutamic-oxalic and glutamic-pyruvic transaminases and lactic dehydrogenase did not increase. Hepatic glutathione (GSH) levels were not significantly altered by 3,4,3',4'-TCB or 3,4,5,3',4',5'-HCB, indicating that GSH depletion does not have a significant role in the production of hepatotoxic changes by PCBs. Measurement of the degree of pathologic change indicated that 3,4,3',4'-TCB and 3,4,5,3',4',5'-HCB were three to four orders of magnitude more potent than 2,4,5,2',4',5'-HCB both as hepatotoxins and as inducers of the cytochrome P-448 mediated mixed function oxidases, aryl hydrocarbon hydroxylase, and 7-ethoxyresorufin deethylase. 2,3,6,2',3',6'-HCB was inactive as an inducer as well as as a hepatotoxin. The findings indicate that hepatotoxic changes are selectively produced in the chick embryo by those PCBs that also induce cytochrome P-448 mediated mixed function oxidases and in that respect resemble other manifestations of PCB toxicity (e.g., subcutaneous and pericardial edema and thymic involution) in both the chicken and other species. The results support the hypothesis that a common initial mechanism leads both to cytochrome P-448 type induction and to diverse manifestations of polyhalogenated hydrocarbon toxicity.
给鸡胚注射四种高度纯化的多氯联苯（PCB）同系物后，对肝脏组织学变化和混合功能氧化酶的诱导情况进行了检测和比较，这四种同系物分别是：3,4,3',4'-四氯联苯（TCB）以及3,4,5,3',4',5'-、2,4,5,2',4',5'-和2,3,6,2',3',6'-六氯联苯（HCB）。主要的组织病理学变化是肝细胞肿胀，表现为肝血窦变窄。在给PCB后24小时内即可观察到这种变化，对于3,4,3',4'-TCB和3,4,5,3',4',5'-HCB，剂量低至5 nmol/蛋时就会出现；而对于2,4,5,2',4',5'-HCB，仅在剂量为5000 nmol/蛋及更高时才会出现。2,3,6,2',3',6'-HCB无活性。组织病理学变化主要分布在血管周围，同时伴有肝脏含水量增加。偶尔可见肝细胞核固缩和胞质嗜酸性变，但几乎没有明显坏死的组织学证据，也没有生化证据，因为血清谷草转氨酶、谷丙转氨酶和乳酸脱氢酶并未升高。3,4,3',4'-TCB或3,4,5,3',4',5'-HCB并未显著改变肝脏谷胱甘肽（GSH）水平，这表明GSH耗竭在PCB产生肝毒性变化过程中不起重要作用。对病理变化程度的测定表明，作为肝毒素以及作为细胞色素P - 448介导的混合功能氧化酶、芳烃羟化酶和7 - 乙氧基异吩恶唑酮脱乙基酶的诱导剂，3,4,3',4'-TCB和3,4,5,3',4',5'-HCB的效力比2,4,5,2',4',5'-HCB高3至4个数量级。2,3,6,2',3',6'-HCB作为诱导剂和肝毒素均无活性。研究结果表明，在鸡胚中，那些能诱导细胞色素P - 448介导的混合功能氧化酶的PCB会选择性地产生肝毒性变化，在这方面类似于鸡和其他物种中PCB毒性的其他表现（如皮下和心包水肿以及胸腺退化）。这些结果支持了这样一种假说，即一种共同的初始机制既导致细胞色素P - 448类型的诱导，也导致多卤代烃毒性的多种表现。
