Enhanced cytochrome P450 capacities of Caco-2 and Hep G2 cells in new coculture system under the static and perfused conditions: evidence for possible organ-to-organ interactions against exogenous stimuli

Enhanced cytochrome P450 capacities of Caco-2 and Hep G2 cells in new coculture system under the static and perfused conditions: evidence for possible organ-to-organ interactions against exogenous stimuli
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DOI:
10.1016/j.msec.2003.12.002
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发表时间:
2004-04-01
期刊:
MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS
影响因子:
--
通讯作者:
Sakai, Y
Sakai, Y
中科院分区:
其他
文献类型:
--
作者:
Choi, SH;Fukuda, O;Sakai, Y

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为了特别研究针对外源性刺激的器官间相互作用,使用了两种共培养系统,即一种简单的双层静态共培养系统和一种由Caco - 2和Hep G2细胞组成的灌注共培养系统,以模拟小肠和肝脏中发生的代谢过程。通过测量细胞色素P450(CYP)1A1/2的诱导作用来评估Caco - 2和Hep G2细胞对受试化学物质的代谢能力。在这两种共培养系统中,就乙氧基试卤灵O - 脱甲基酶(EROD)活性而言,苯并[a]芘(B[a]P)或3 - 甲基胆蒽(3 - MC)对CYP1A1/2的诱导作用比单个细胞培养所预期的更为显著。这似乎表明在人体对外源性刺激的生理保护方面可能存在器官间的相互作用。因此,我们可以说实时联合系统对于预测人体中的复杂现象确实非常重要,因为单个培养系统无法体现器官间的相互作用,而且共培养系统能够提供许多复杂现象所导致的最终代谢活性的信息。(C)2004爱思唯尔公司。版权所有。
To investigate particularly organ-to-organ interactions against the exogenous stimuli, two coculture systems, i.e. a simple double-layered static coculture system and a perfusion coculture system consisting of Caco-2 and Hep G2 cells to mimic the metabolic processes occurring in the small intestine and the liver, were used. The induction of cytochrome P450 (CYP) 1A1/2 was measured to estimate the metabolic capacity of Caco-2 and Hep G2 cells against tested chemicals.In both coculture systems, the inducibility of CYP1A1/2 by benzo[a]pyrene (B[a]P) or 3-methylcholanthrene (3-MC) in terms of ethoxyresorufin O-dimethylase (EROD) activity was more remarkable than expected from the individual cell cultures. It seemed to show possible organ-to-organ interactions in terms of the physiological protection of human body against exogenous stimuli. Therefore, we can say that a real-time combined system is really important to predict the complicated phenomena in human because an individual culture system cannot represent the organ-to-organ interaction and also coculture systems can give information of final metabolic activity as a result of many complicated phenomena. (C) 2004 Elsevier B.V. All rights reserved.