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

Journal Article · Sun Nov 15 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.002· OSTI ID:21344787

Betanzos, Abigail; Weber, Dominique A; Nava, Porfirio ^[1]; Miller, Gary W ^[2]

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1. Department of Pathology and Laboratory Medicine, Epithelial Pathobiology Research Unit, Emory University, Atlanta, GA 30322 (United States)
2. Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322 (United States)

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.

• OSTI ID: 21344787
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 1; Other Information: DOI: 10.1016/j.taap.2009.08.002; PII: S0041-008X(09)00328-7; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL MEMBRANES
DEXTRAN
DOSES
EPITHELIUM
IN VITRO
INTESTINES
IODIDES
MEN
PHENOL
PROTEINS
TOXICITY
TRYPAN BLUE
AMINES
ANIMAL TISSUES
ANIMALS
AROMATICS
AZO COMPOUNDS
AZO DYES
BLOOD SUBSTITUTES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
DIGESTIVE SYSTEM
DRUGS
DYES
GASTROINTESTINAL TRACT
HALIDES
HALOGEN COMPOUNDS
HEMATOLOGIC AGENTS
HYDROXY COMPOUNDS
IODINE COMPOUNDS
MALES
MAMMALS
MAN
MEMBRANES
NAPHTHOLS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHENOLS
POLYSACCHARIDES
PRIMATES
SACCHARIDES
SULFONIC ACIDS
VERTEBRATES