Phenol toxicity and conjugation in human colonic epithelial cells.
BACKGROUND
Colonic epithelial cells are exposed to a range of potentially harmful luminal factors. including phenols, but it is unresolved whether these compounds impair the integrity of the epithelium. The aim of this study was to describe the effect of phenol exposure on human colonic epithelial cells in vitro and the conjugation pathways involved in detoxification.


METHODS
Primary human colonic epithelial cell cultures or HT-29 cell cultures were exposed to paracetamol, dinitrophenol or phenol (0.1-5 mM) for 24 h. Cell viability was measured using the methyltetrazoleum test. Phenol conjugation products released from cell cultures were identified by high-pressure liquid chromatography. Phenol glucuronidase (PGD) and sulphotransferase (PST) enzyme activities were measured in isolated cell homogenates.


RESULTS
Paracetamol, dinitrophenol and phenol (>1.25 mM) significantly impaired the viability of primary colonic epithelial cell cultures. No differences between cell cultures from ulcerative colitis and control patients were observed. Paracetamol (5 mM) also induced significant cell damage in HT-29 cells. Glucuronidation was the preferred conjugation pathway in both cell models, despite the presence of PGD and PST activity.


CONCLUSIONS
Phenols have a direct toxic effect on human colonic epithelial cells in vitro, which supports the view that dietary fermentation metabolites may be involved in the modulation of chronic bowel inflammation.
Pedersen
G
G
Dept of Medical Gastroenterology, Herlev University Hospital, Copenhagen, Denmark. giped@dadlnet.dk
Brynskov
J
J
Saermark
T
T
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003227:Conjugation, Genetic / Q000187:drug effects*; D004202:Disinfectants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019800:Phenol / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
D004202:Disinfectants; D019800:Phenol