Effect of fatty acids and the aqueous diffusion barrier on the uptake and transport of polychlorinated biphenyls in Caco-2 cells

Abstract

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.