Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats.
Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment 1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.
Verghese
M
M
Nutrition and Carcinogenesis Laboratory, Department of Food and Animal Sciences, Alabama A&M University, Normal, AL 35762, USA. mverghese@aamu.edu
Rao
D R
DR
Chawan
C B
CB
Shackelford
L
L
D000367:Age Factors; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002432:Cecum / Q000737:chemistry / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004043:Dietary Fiber / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007444:Inulin / Q000008:administration & dosage*; D008297:Male; D009929:Organ Size; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D004043:Dietary Fiber; D007444:Inulin; D001397:Azoxymethane