Polyethylene glycol, unique among laxatives, suppresses aberrant crypt foci, by elimination of cells.

Abstract

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.