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Journal of Lipid Research, Vol 37, 950-961, Copyright © 1996 by Lipid Research, Inc.
WJ Dulfer, JP Groten and HA Govers
Polychlorinated biphenyls (PCBs) dissolved in dietary fat are absorbed in
the gastrointestinal tract by the enterocytes in combination with the fatty
acids proceeding from the lipid hydrolysis in the gut lumen. The effect of
fatty acid absorption on the uptake and transport of 14 PCBs in enterocytes
was studied using monolayers of the human intestinal Caco-2 cell line as a
model system. The diffusive resistance of the unstirred water layer and the
facilitating role of mixed bile salt micelles on the PCB uptake were
examined by varying the thickness of the unstirred water layer adjacent to
the apical membrane. In additional experiments, the polarity of the PCB
uptake and transport in Caco-2 cells was determined. The solubility of PCBs
in the mixed bile salt-fatty acid micelles was 2.7 to 4.8-fold higher than
the solubility in plain bile salt micelles. Both the uptake and transport
of PCBs in Caco-2 cells were significantly higher (up to 10-fold) when the
PCBs were presented mixed with fatty acids. Reducing the thickness of the
unstirred water layer resulted in an increased uptake of PCBs. The PCB
uptake in Caco-2 cells exceeded the uptake as expected from monomer
diffusion only, indicating that bile salt micelles facilitate the PCB
transport over the unstirred water layer. Concentrations of
dichlorobiphenyls accumulating in the basolateral medium stayed
unexpectedly low, suggesting that Caco-2 cells might possess the capability
of metabolizing lower chlorinated biphenyls. Uptake of PCBs into the Caco-2
cells was not significantly different whether the PCBs were presented at
the apical side or at the basolateral side. However, transport of PCBs over
the cell monolayer was significantly higher when the PCBs were presented at
the apical side as compared to the basolateral side, suggesting that the
unidirectional transport of lipids and lipoproteins affected the PCB
transport as well. Our studies indicate that monolayers of the Caco-2 cell
line offer a useful model system for studying the intestinal uptake and
transport processes of hydrophobic xenobiotics such as polychlorinated
biphenyls.
ARTICLES
Effect of fatty acids and the aqueous diffusion barrier on the uptake and transport of polychlorinated biphenyls in Caco-2 cells
Department of Environmental and Toxicological Chemistry, University of Amsterdam, The Netherlands.
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