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Author Notes:

Correspondence: Ingrid C. McCall and Charles A. Parkos, Department of Pathology and Laboratory Medicine, Whitehead Biomedical Research Building, Room 115, Emory University, 615 Michael Street, Atlanta, GA 30322, USA. Fax: 1-404-727-8538; Email: ingridmccall@yahoo.com, icmccal@emory.edu, and cparkos@emory.edu

Acknowledgments: We thank Dr. Susan Voss for expert cell culture, Dr. Michael Schnoor, and Dr. Neal Beeman, and Dr. Christopher Capaldo for scientific advice.

Disclosures: This research was performed in partial fulfillment of a MPH degree at Rollins School of Public Health at Emory University.


Research Funding:

This work was supported by the National Institutes of Health DK72564 and DK61379 (C.A.P), a Digestive Diseases Minicenter grant DK064399 (epithelial cell culture core and microscopy core support), and the Crohn's and Colitis Foundation of America (P. Nava).


  • Phenol
  • SK-CO15 cells
  • Transepithelial electrical resistance
  • Tight junctions
  • Epithelial paracellular barrier
  • Cell viability

Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization


Journal Title:

Toxicology And Applied Pharmacology


Volume 241, Number 1


, Pages 61-70

Type of Work:

Article | Post-print: After Peer Review


Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist. We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining. Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.

Copyright information:

© 2009 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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