Wheat aleurone flour increases cecal beta-glucuronidase activity and butyrate concentration and reduces colon adenoma burden in azoxymethane-treated rats.

Processed wheat aleurone flour (WAF) is a source of insoluble fermentable dietary fiber that comes from the outer layers of the wheat kernel. A study was designed to evaluate WAF, wheat bran (WB) and alpha-cellulose as the source of dietary fiber (5 g/100 g of diet) in a semipurified high fat (20 g/100 g of as 1:1 lard/sunflower seed oil) diet fed to male Sprague-Dawley rats in which intestinal tumors were induced using azoxymethane (AOM). WAF at 33 g/100 g of diet (WAF33) and WB at 16 g/100 g of diet (WB16) increased the weight of feces and produced significantly higher concentrations in the cecum of the short-chain fatty acid butyrate (P < 0.001) than did no fiber (NF) and WAF added at only 10 g/100 g (1.5 g of dietary fiber) (WAF10). Cecal and fecal pH were both significantly lower in the WAF33 and WB16 treatments relative to control and no fiber treatments (P < 0.001). The intestinal tumors in the rats were assessed at 6 mo after the study began, and the WAF33- or WB16-fed rats showed a trend (P = 0.06) with 43% fewer colon adenomas relative to control. There was a significant inverse relationship between ss-glucuronidase activity and colon adenomas in the rat colon (r2 = 0.37, P = 0.001). WAF fiber influenced some metabolic markers of fermentation in the colon in a manner similar to that of WB, which, independent of the bulking effect, was associated with a trend to reduced colon adenomas. Significantly increased cecal ss-glucuronidase activity and/or butyrate concentrations may have protective influences in this context by mechanisms not yet fully elucidated.

A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p < 0.05). Other treatments showed no statistically significant change from control for these indexes of tumorigenesis. For rats fed L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

A diet containing chickpeas and wheat offers less protection against colon tumors than a casein and wheat diet in dimethylhydrazine-treated rats.

We examined the influence of extruded chickpeas and wheat relative to casein and wheat in a dimethylhydrazine (DMH)-induced colon tumor study in male Sprague-Dawley rats. The three diets, based on a modified AIN76 rodent diet with fat present at 10 g/100 g dry matter (DM), were as follows: casein with wheat starch (Cas/S) as control, casein with wheat (Cas/W) and chickpeas with wheat (CP/W). All diets were fed from 5 wk of age throughout the 28-wk study. At 28 wk, there was a significantly lower incidence of large intestinal tumors in rats fed Cas/W relative to those fed CP/W ( 11 vs. 56%, chi-square test, P = 0.018). The colonic tumor burden (tumors/tumor-bearing animal) was not different in Cas/W-fed and CP/W-fed rats (1 vs. 1.7), but the tumor mass index was significantly lower in the former group (0.22 vs. 1.21, P = 0.026). Rats fed the CP/W diet had significantly lower plasma cholesterol concentration (P < 0.01) than rats fed the other two diets. The cecal contents of rats fed the CP/W diet had significantly greater relative weights (46%, P < 0.05) than those of the Cas/W-fed rats; this was associated with higher concentrations of all short-chain fatty acids. Fecal analyses showed significantly (P < 0.05) higher concentrations of total fat (54%), total steroids (83%) and secondary bile acids (179%) in the CP/W-fed rats relative those fed Cas/W. There were higher concentrations of nitrogen in the feces of CP/W rats relative to the Cas/W-fed rats (84%, P < 0.05), associated with greater fecal weights (67%, P < 0.05). Although wheat and its fibers have been shown to be protective against DMH-induced cancers in rats, this was not the case in this study in which chickpeas (45 g/100 g diet) provided the protein and were an important source of soluble fiber. Elevated fat, secondary bile acid concentrations and/or nitrogenous compounds could be responsible for the increased colon tumorigenesis seen and may reflect a legume effect.

A comparative study of the influence of differing barley brans on DMH-induced intestinal tumours in male Sprague-Dawley rats.

The influence of barley brans on the incidence and burden of intestinal tumours in rats induced by 1,2-dimethylhydrazine (DMH) was studied in a 7 month feeding experiment. The basic diet was American Institute of Nutrition (AIN) 76 modified by adjustment to 20% fat and 40% starch; brans were added so as to supply 5% dietary fibre. The barley brans studied were commercial barley bran (BB1; 13.0% dietary fibre) from the aleurone/subaleurone layer, outerlayer barley bran (BB2) including the germ (25.5% dietary fibre) and spent barley grain bran (SBG; a by-product of the brewery and including the hull; 47.7% dietary fibre). They were compared with wheat bran (WB; 44% dietary fibre) and cellulose (or control; 98% dietary fibre). Commercial barley bran and wheat bran were most effective in reducing tumour incidence and burden. The incidence of tumours fell significantly from 70% (BB2) and 50% (SBG) to 10% (BB1) and 20% (WB) and tumour burden and tumour mass index (TMI) were also reduced by similar orders of magnitude. There were significantly higher short chain fatty acid (SCFA) concentrations in WB- and BB1-fed rat faecal pellets relative to cellulose- and BB2-fed rat faeces; butyrate, in particular, was affected. Regression analysis of butyrate against tumour incidence showed a trend (r = 0.898: P = 0.055), but the concentration of butyrate alone could not account for the reduction in tumour incidence observed. In a second experiment, when two brans (BBI and SBG) were introduced after DMH dosing, there were higher incidences and burdens of tumours, indicating that protection by such brans was not as effective under these circumstances. Commercially available barley bran and wheat bran appear to significantly reduce tumour incidence and burden in this model relative to other brans, influencing both the initiatory as well as promotional stages of chemically induced carcinogenesis.

Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats.

The impact of different dietary protein sources (whey, casein, soybean, red meat) on the incidence, burden and mass index of intestinal tumors induced by dimethylhydrazine in male Sprague-Dawley rats was assessed. A purified diet (based on AIN-76A) with a fat concentration of 20 g/100 g and other proteins substituted for casein (20 g/100 g) was used. Whey and casein diets were more protective against the development of intestinal tumors than were the red meat or soybean diets, as evidenced by a reduced incidence of rats affected (P = 0.15), fewer tumors per treatment group (burden, P < 0.005), and a reduced pooled area of tumors (tumor mass index) that formed (P = 0.39). Intracellular concentration of glutathione, an antioxidant and anticarcinogenic tripeptide, measured in liver, was greatest in whey protein- and casein-fed rats and lowest in soybean-fed animals (P < 0.001). For other tissues (spleen, colon, tumor) the differences were not significant, although the whey-fed animals had the highest concentrations of glutathione (P = 0.8). Whey is a source of precursors (cysteine-rich proteins) for glutathione synthesis and may be important in providing protection to the host by stimulating glutathione synthesis. A positive correlation was observed between mean fecal fat concentrations for rats in each treatment group and large intestinal tumor burden (r2 = 0.898, P = 0.05). Fecal fat could be involved in aiding initiation and/or promotion of carcinogenesis. Whatever the mechanism(s), dairy proteins, and whey proteins in particular, offer considerable protection to the host against dimethylhydrazine-induced tumors relative to the other protein sources examined.