Polyethylene glycol reduces inflammation and aberrant crypt foci in carcinogen-initiated rats.
Polyethylene glycol 8000 inhibits the formation of tumors and of aberrant crypt foci (ACF) in carcinogen-initiated rats. We asked: is the inhibition associated with a reduction of colonic inflammation and an increase in colonic cell permeability? Twenty-eight, male F 344 rats were divided into two groups, 10 control animals and 18 animals initiated with azoxymethane. Nine of the rats in the carcinogen-initiated group were given a diet with 5% PEG 8000 in an AIN-93 based, high fat diet. The other nine, and the control group received the diet without the addition of PEG. Nine weeks later, the rats receiving the diet containing PEG had a 43% reduction in ACF (P<0.001) compared with the carcinogen-initiated rats on the control diet, a result confirming earlier observations that PEG inhibits colon carcinogenesis. The animals receiving the diet containing PEG also had a 10-fold reduction in fecal granulocyte marker protein (GMP) (P<0.001) compared with both the carcinogen-treated and the control animals. PEG reduced inflammation below the levels of carcinogen-treated and of untreated animals. Fecal water from the rats receiving PEG did not reduce transepithelial resistance of, or manitol flux through, human Caco-cells grown as monolayers in vitro. PEG may reduce colon carcinogenesis through a mechanism involving colonic inflammation.
Karlsson
Pernilla C
PC
Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden.
Hughes
Roisin
R
Rafter
Joseph J
JJ
Bruce
W Robert
WR
D000284:Administration, Oral; D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage / Q000633:toxicity; D018938:Caco-2 Cells; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control* / Q000662:veterinary; D006801:Humans; D007249:Inflammation; D008297:Male; D010539:Permeability; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000494:pharmacology*
D002273:Carcinogens; D012997:Solvents; D011092:Polyethylene Glycols; D001397:Azoxymethane