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

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.