Thomé J P, Roelandt L, Goffinet G, Stouvenakers N, Kremers P
Laboratoire d'Ecotoxicologie des Milieux Terrestres et Aquatiques, Institut de Zoologie, Liege, Belgium.
Toxicology. 1995 Apr 12;98(1-3):83-94. doi: 10.1016/0300-483x(94)02793-t.
The cytotoxicity of a commercial PCB mixture, Aroclor 1254, was assessed on cultured foetal rat hepatocytes. Under control conditions, dexamethasone stimulates immature hepatocytes to differentiate into both hepatocytes and biliary epithelial cells. Consequently, foetal rat hepatocytes maintain, in vitro, a liver-like organization with spaces corresponding to the lumen of biliary canalicules, many mitochondria, and a well-developed rough endoplasmic reticulum (RER). This in vivo-like organization of cultured rat hepatocytes remains unchanged in medium supplemented with Aroclor 1254 at concentrations below 25 microM. In the 25-125 microM concentration range, however, PCBs severely alter some cellular organelles, notably causing important development of the RER and the appearance of cytoplasmic lacunae containing laminated concentric membrane arrays. In addition, the number of lipid droplets increases, the glycogen islets disappear, and dramatic local alterations of the mitochondrial cristae occur. In exposed and unexposed cells, the following biochemical parameters were measured: the DNA content, protein synthesis, lipid peroxidation, and urea formation. The results show that Aroclor 1254 at concentrations exceeding 25 microM (but not at lower concentrations) causes irreversible damage to cultured hepatocytes. The observed ultrastructural modifications are in good agreement with several in vivo studies on rat liver. Thus, isolated foetal rat hepatocytes have considerable potential as an alternative to whole animals for use in (eco)toxicological studies.
对一种商用多氯联苯混合物Aroclor 1254在培养的胎鼠肝细胞上的细胞毒性进行了评估。在对照条件下，地塞米松刺激未成熟肝细胞分化为肝细胞和胆管上皮细胞。因此，胎鼠肝细胞在体外维持着类似肝脏的组织结构，具有对应胆小管腔的间隙、许多线粒体和发达的粗面内质网（RER）。在添加浓度低于25微摩尔的Aroclor 1254的培养基中，培养的大鼠肝细胞的这种类似体内的组织结构保持不变。然而，在25 - 125微摩尔的浓度范围内，多氯联苯会严重改变一些细胞器，特别是导致粗面内质网的显著发育以及出现含有层状同心膜阵列的细胞质腔隙。此外，脂滴数量增加，糖原岛消失，线粒体嵴出现明显的局部改变。对暴露和未暴露的细胞测量了以下生化参数：DNA含量、蛋白质合成、脂质过氧化和尿素形成。结果表明，浓度超过25微摩尔（但较低浓度时不会）的Aroclor 1254会对培养的肝细胞造成不可逆损伤。观察到的超微结构改变与对大鼠肝脏的多项体内研究结果高度一致。因此，分离的胎鼠肝细胞作为全动物的替代物在（生态）毒理学研究中具有相当大的潜力。
