A two-compartment cell culture system using Caco-2 and Hep G2 cells for mimicking absorption and biotransformation processes in humans : Application to the analysis of benzo[a]pyrene toxicity

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概要

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• A simple double-layered cell culture system using Caco-2 cells and Hep G2 cells, which mimic the metabolic processes occurring in humans such as adsorption through the small intestine and biotransformation in both the small intestine and the liver cells, was developed to investigate the toxicity of hazardous materials in humans. In the double-layered culture system, the inducibility of cytochrome P450 1A1/2 by 3-methylcholanthrene in terms of ethoxyresorufin O-dimethylase (EROD) activity was more remarkable than expected from the individual cell cultures (total activity of two single-population cultures). It seemed to show possible organ-to-organ interactions in terms of the physiological protection of human body against exogenous stimuli. Although the total cytochrome P450 1A1/2 capacity was enhanced in the double-layered system, when we loaded 50 _M of BaP to the apical side (AP) of the Caco-2 cell layer, HPLC analysis of BaP and its metabolites including the precursor of the ultimate carcinogen of BaP, 7,8-diol, showed decreased concentration of 7,8-diol in the basolateral (BL) side, which was well correlated with lower cytotoxicity in the double-layered system in terms of the cell viability and albumin secretion of Hep G2 cells. Therefore, a double-layered system can give more confidential information of the toxic actions of the hazardous chemicals in human than a monolayered system, because the double-layered system can give information of final toxicity as a result of many complicated phenomena.

• 一般社団法人日本機械学会の論文

著者

• Choi S.

  Institute Of Industrial Science University Of Tokyo

• Fukuda O.

  Institute of Industrial Science, University of Tokyo

• Iwahashi H.

  The National Institute of Advanced Industrial Science and Technology

• Momose Y.

  The National Institute of Advanced Industrial Science and Technology

• Sakoda A.

  Institute of Industrial Science, University of Tokyo

• Sakai Y.

  Institute of Industrial Science, University of Tokyo

• Sakoda A.

  Institute Of Industrial Science University Of Tokyo

関連論文

• A two-compartment cell culture system using Caco-2 and Hep G2 cells for mimicking absorption and biotransformation processes in humans : Application to the analysis of benzo[a]pyrene toxicity
• Rapid immobilization of liver-derived cells and its application to the identification of a minimum number of cells necessary for liver-cell array
• Construction of a three-dimensional heterogeneous micro-tissue toward the evaluation of a minimum required size
• Development of a cocultivation microdevice for toxicokinetic study in humans

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