Perrot N, Chesné C, De Waziers I, Conner J, Beaune P H, Guillouzo A
Institut National de la Santé et de la Recherche Médicale Unité 75, Centre Hospitalo-Universitaire Necker-Enfants-Malades, Paris, France.
Eur J Biochem. 1991 Aug 15;200(1):255-61. doi: 10.1111/j.1432-1033.1991.tb21074.x.
Cultured and cocultured rat hepatocytes were used to study the effects of ethanol and clofibrate on cytochrome P-450 (P-450) enzymes and epoxide hydrolase. We showed that in the presence of ethanol, clofibrate or both compounds, rat hepatocytes were able to express, after 3 days of pure culture, quantitatively and qualitatively reasonable levels of most cytochrome P-450 enzymes and epoxide hydrolase, compared to freshly isolated hepatocytes. However, ethanol induced the P-450IA subfamily, and clofibrate the P-450-IVA subfamily. In cocultures, after 6 days, most P-450 enzymes were still expressed while P-450IIC11 was completely lost. Ethanol and clofibrate had the same effect as in pure culture. These results show, by modifying culture medium conditions and cell-cell interactions, that it is possible to maintain reasonable xenobiotic-metabolizing-enzyme expression; however, these conditions have to be improved in order to preserve better P-450 expression. The mechanism of these effects and the inducibility of these systems remain to be elucidated by a study at molecular level.
使用培养的和共培养的大鼠肝细胞来研究乙醇和氯贝丁酯对细胞色素P-450（P-450）酶和环氧化物水解酶的影响。我们发现，在存在乙醇、氯贝丁酯或两种化合物的情况下，与新鲜分离的肝细胞相比，大鼠肝细胞在纯培养3天后能够定量和定性地表达合理水平的大多数细胞色素P-450酶和环氧化物水解酶。然而，乙醇诱导P-450IA亚家族，氯贝丁酯诱导P-450-IVA亚家族。在共培养6天后，大多数P-450酶仍有表达，而P-450IIC11完全丧失。乙醇和氯贝丁酯的作用与在纯培养中相同。这些结果表明，通过改变培养基条件和细胞间相互作用，可以维持合理的外源性物质代谢酶表达；然而，为了更好地保留P-450表达，这些条件必须加以改善。这些作用的机制以及这些系统的诱导性仍有待在分子水平上进行研究以阐明。
