Kremers P, Roelandt L, Stouvenakers N, Goffinet G, Thome J P
Universite de Liège, Laboratoire de Chimie Médicale, Sart Tilman, Belgium.
Cell Biol Toxicol. 1994 Apr;10(2):117-25. doi: 10.1007/BF00756492.
An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were expressed in these hepatocytes, namely, testosterone hydroxylations. Hepatocytes cultured up to 3 weeks in the presence of dexamethasone and phenobarbital still expressed some drug-metabolizing enzyme activities (e.g., ECOD). The enzymatic activities were measured both directly on monolayers during culture and on the corresponding harvested and homogenized cells. The results correlate perfectly with each other. The 'on cell' procedure allows us to repeat the assay or to measure several activities on the same cells at different time intervals. The presence of dexamethasone in the culture medium allows the expression and the induction of several cytochrome P450 isoenzymes, namely, those hydroxylating testosterone. This makes the model particularly attractive for induction experiments as well as for metabolic or toxicological studies needing longer treatments.
一种体外实验模型,即培养的胎鼠肝细胞,进行了代谢特性分析。这些肝细胞表达了几种酶活性,即睾酮羟化酶活性。在存在地塞米松和苯巴比妥的情况下培养长达3周的肝细胞仍表达一些药物代谢酶活性(例如,乙氧黄酮脱乙基酶)。酶活性在培养期间直接在单层细胞上以及在相应收获并匀浆的细胞上进行测量。结果彼此完美相关。“细胞上”操作使我们能够重复测定或在不同时间间隔对同一细胞测量几种活性。培养基中地塞米松的存在允许几种细胞色素P450同工酶的表达和诱导,即那些使睾酮羟化的同工酶。这使得该模型对于诱导实验以及需要更长时间处理的代谢或毒理学研究特别有吸引力。