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2006 ; 41
(6
): 730-6
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Polyethylene glycol, unique among laxatives, suppresses aberrant crypt foci, by
elimination of cells
#MMPMID16716974
Taché S
; Parnaud G
; Van Beek E
; Corpet DE
Scand J Gastroenterol
2006[Jun]; 41
(6
): 730-6
PMID16716974
show ga
OBJECTIVE: Polyethylene glycol (PEG), an osmotic laxative, is a potent inhibitor
of colon cancer in rats. In a search for the underling mechanisms, the hypothesis
that fecal bulking and moisture decrease colon carcinogenesis was tested. We also
investigated the PEG effects on crypt cells in vivo. MATERIAL AND METHODS:
Fischer 344 rats (n=272) were injected with the colon carcinogen, azoxymethane.
They were then randomized to a standard AIN76 diet containing one of 19 laxative
agents (5% w/w in most cases): PEG 8000 and other PEG-like compounds,
carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, calcium
polycarbophil, karaya gum, psyllium, mannitol, sorbitol, lactulose, propylene
glycol, magnesium hydroxide, sodium phosphate, bisacodyl, docusate, and paraffin
oil. Aberrant crypt foci (ACF) and fecal values were measured blindly after a
30-day treatment regimen. Proliferation, apoptosis, and the removal of cells from
crypts were studied in control and PEG-fed rats using various methods, including
TUNEL and fluorescein dextran labeling. RESULTS: PEG 8000 reduced the number of
ACF 9-fold in rats (p<0.001). The other PEGs and magnesium hydroxide modestly
suppressed ACF, but not the other laxatives. ACF number did not correlate with
fecal weight or moisture. PEG doubled the apoptotic bodies per crypt (p<0.05),
increased proliferation by 25-50% (p<0.05) and strikingly increased (>40-fold) a
fecal marker of epitheliolysis in the gut (p<0.001). PEG normalized the
percentage of fluorescein dextran labeled cells on the top of ACF (p<0.001).
CONCLUSIONS: Among laxatives, only PEG afforded potent chemoprevention. PEG
protection was not due to increased fecal bulking, but in all likelihood to the
elimination of cells from precancerous lesions.
|Animals
[MESH]
|Azoxymethane/toxicity
[MESH]
|Carcinogens/toxicity
[MESH]
|Cathartics/*pharmacology/therapeutic use
[MESH]
|Colonic Neoplasms/chemically induced/*prevention & control
[MESH]
|Feces/chemistry
[MESH]
|Polyethylene Glycols/*pharmacology/therapeutic use
[MESH]
|Precancerous Conditions/chemically induced/*prevention & control
[MESH]