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This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by C[O.sub.2] at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by ~4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage. KEY WORDS: * azoxymethane * aberrant crypt foci * inulin * colon tumors * 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. KEY WORDS: * aberrant crypt foci * azoxymethane * colon carcinogenesis * inulin * mature rats *

Anticarcinogenic properties of phytic acid [inositol hexaphosphate (I[P.sub.6])], a natural dietary constituent present in grains, is gaining considerable importance. The objective of this study was to test the effect of I[P.sub.6] and inositol, both singly and in combination, at levels of 1 and 2% on azoxymethane-induced colonic aberrant crypt foci (ACF), which are preneoplastic lesions in Fisher 344 male rats. Six groups (n = 15/group) of Fisher 344 male weanling rats were assigned to AIN 93G (control; C), C + 1 or 2% I[P.sub.6], C + 1 or 2% inositol and C + 1% I[P.sub.6] + 1% inositol in water. All rats were fed 16 mg/kg body of azoxymethane dissolved in saline subcutaneously at age 7 wk followed by a second injection at age 8 wk. The animals were killed at age 17 wk. Inositol when fed in combination with I[P.sub.6] protected against the decrease in weight gain observed in the group fed 2% I[P.sub.6] alone. Results showed a significant (P < 0.05) reduction of colonic ACF. The group fed 1% I[P.sub.6] + 1% inositol showed a 42.7% reduction in total ACF compared with reductions of 32.5 and 42.1% for 1 and 2% I[P.sub.6] and 18.6 and 32.3% for 1 and 2% inositol, respectively. Although inositol acted by itself in reducing colonic ACF, it appeared to enhance the action of I[P.sub.6] and reduce the amount of I[P.sub.6] required by 50%. The results of this study indicate that inositol given in combination with I[P.sub.6] suppressed azoxymethane-induced ACF formation, an early preneoplastic marker in the process of colon carcinogenesis in Fisher 344 male rats.