Ottenwälder H, Kappus H, Bolt H M
Arch Toxicol Suppl. 1983;6:266-70. doi: 10.1007/978-3-642-69083-9_49.
Proteins of isolated rat hepatic sinusoidal cells incubated with 14C-vinyl chloride, rat liver microsomes and an NADPH-regenerating system were alkylated by vinyl chloride metabolites formed by microsomes. This suggests that reactive vinyl chloride metabolites can penetrate sinusoidal cells. Protein alkylation in isolated hepatic sinusoidal cells was higher when these were co-incubated with isolated hepatocytes, indicating that reactive vinyl chloride metabolites formed by hepatocytes are stable enough to diffuse out of hepatocytes into sinusoidal cells. Glutathione added to the incubation medium inhibited the covalent protein binding of vinyl chloride metabolites in sinusoidal cells as well as in hepatocytes incubated separately and deleted the increased protein binding in sinusoidal cells co-incubated with hepatocytes. The data indicate that glutathione present in the incubation medium traps reactive vinyl chloride metabolites formed by hepatocytes which otherwise would react with cell constituents of sinusoidal cells. If similar conditions exist in vivo, the alkylation of DNA of liver endothelial cells by vinyl chloride metabolites formed in hepatocytes is possible. This would explain the induction of hemangioendotheliomas of the liver by vinyl chloride.
将分离出的大鼠肝窦状细胞与14C - 氯乙烯、大鼠肝微粒体及NADPH再生系统一起孵育，微粒体形成的氯乙烯代谢产物会使这些细胞的蛋白质发生烷基化。这表明具有反应活性的氯乙烯代谢产物能够穿透肝窦状细胞。当分离出的肝窦状细胞与分离出的肝细胞共同孵育时，其蛋白质烷基化程度更高，这表明肝细胞形成的具有反应活性的氯乙烯代谢产物足够稳定，能够从肝细胞扩散到肝窦状细胞中。向孵育培养基中添加谷胱甘肽可抑制肝窦状细胞以及单独孵育的肝细胞中氯乙烯代谢产物与蛋白质的共价结合，并消除与肝细胞共同孵育的肝窦状细胞中增加的蛋白质结合。数据表明，孵育培养基中的谷胱甘肽会捕获肝细胞形成的具有反应活性的氯乙烯代谢产物，否则这些代谢产物会与肝窦状细胞的细胞成分发生反应。如果体内存在类似情况，肝细胞中形成的氯乙烯代谢产物有可能使肝内皮细胞的DNA发生烷基化。这将解释氯乙烯对肝血管内皮瘤的诱发作用。
