Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice.
Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice.
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四氯乙烯处理小鼠中三氯酰化蛋白加合物的免疫组织化学定位。
DOI：
10.1080/15287390151126487
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Ansari,GA
中科院分区：
文献类型：
--
作者：
Green,SM;Khan,MF;Kaphalia,BS;Ansari,GA
四氯乙烯（PCE）是一种常见的工业溶剂和环境污染物，主要用于干洗行业。PCE的毒性与视力障碍、肾癌和肝癌以及自身免疫性疾病有关。虽然毒性机制尚未完全了解，但PCE在已知发生毒性的组织中形成三氯酰化蛋白加合物。这些加合物可能通过改变细胞蛋白质的功能而导致毒性。使用蛋白质印迹分析，三氯酰化蛋白质加合物的形成已被报道。为了确定加合物在组织特定区域中的定位，在研究中使用免疫组织化学染色。用兔抗三氯酰化蛋白的抗血清，用酶联免疫吸附试验（ELISA）建立其特异性。雌性MRL-lpr/lpr和MRL +/+小鼠在24 h内或每4天一次给予PCE（5 mmol/kg），持续6周（共20次给药）。在肝脏中观察到三氯酰化蛋白加合物的形成，并定位于小叶中心区。亚慢性给药小鼠中央静脉周围染色的强度和周长远大于急性给药小鼠。在检查的任何其他组织中均未观察到免疫化学反应性。这项研究表明，肝三氯酰化蛋白加合物位于肝脏的一个区域，在那里PCE介导的毒性是已知的发生。这些加合物的免疫组织化学定位及其与PCE诱导的毒性的关联支持加合物可能导致毒性的论点。
Tetrachloroethene (PCE), a common industrial solvent and environmental contaminant, is primarily used in the dry-cleaning industry. The toxicity of PCE has been linked to vision disorders, renal and hepatic cancer, and autoimmune diseases. Although the mechanism of toxicity is not fully understood, PCE forms trichloroacylated protein adducts in tissues where toxicity is known to occur. These adducts may be responsible for toxicity by altering the function of cellular proteins. Using Western blot analysis, formation of trichloroacylated protein adducts has been reported. To determine the localization of the adducts in a specific zone of a tissue, immunohistochemical staining was used in the study. An antiserum to trichloroacylated proteins was raised in rabbits and its specificity was established by enzyme-linked immunosorbent assay (ELISA). Female MRL-lpr/lpr and MRL +/+ mice were treated with PCE using a single 5-mmol/kg dose over 24 h or on every fourth day for 6 wk (total 20 doses). Formation of trichloroacylated protein adducts was observed in the liver, and localized to the centrilobular zones. Intensity and circumference of the staining around the central vein were much greater in subchronically treated mice than in acutely treated mice. No immunochemical reactivity was observed in any of the other tissues examined. This study shows that hepatic trichloroacylated protein adducts are localized in a region of the liver where PCE-mediated toxicity is known to occur. Immunohistochemical localization of these adducts and its association with PCE-induced toxicity support the contention that adducts may contribute to toxicity.