Inhibition of colonic aberrant crypt foci by curcumin in rats is affected by age

Curcumin has antioxidative, anti-inflammatory, and chemopreventive activities. To determine whether aging affects the inhibition of colon carcinogenesis by curcumin, young (6 wk), mature (12 mo), and old (22 mo) F344 male rats were fed either AIN-93 containing 0.6% curcumin or AIN-93 control diet. Aberrant crypt foci (ACF) were induced with two weekly s.c. injections of azoxymethane. After an additional 3 mo on the diets, the number, multiplicity, and distribution of ACF were evaluated. Addition of curcumin to the diet reduced the number of ACF by 49% in young rats and by 55% in old rats (P < 0.05). However, interestingly, no reduction of ACF was found in mature rats fed curcumin. Inhibition of large ACF was also affected by age, with the greatest reduction of large ACF occurring in old rats. However, animal age did not significantly alter the effect of dietary curcumin on reduction of cyclooxygenase-2 mRNA expression in the liver or reduction of serum total cholesterol levels. These results indicate that age may play a significant role in the efficacy of chemoprevention of colon cancer by curcumin.     

Effects of green tea on colonic aberrant crypt foci and proliferative indexes in rats.

The present study was designed to investigate the effect of green tea on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation in Wistar rats. Forty-five male weanling Wistar rats were randomly divided into three groups. Rats in Group 1 were injected with DMH (20 mg/kg s.c.) once a week for 10 weeks. Animals in Group 2 received 2% green tea water extract as the sole source of drinking fluid in addition to the same treatment used for Group 1. Group 3 was the negative control group. Animals were killed at the end of Week 16 after the first DMH treatment. ACF were formed in animals in their DMH-treated groups at the end of Week 16. Group 2 had fewer ACF than Group 1. Compared with the positive control group, proliferating cell nuclear antigen labeling index, silver-stained nucleolar organizer regions, and ras-p21 expression were significantly reduced in Group 2. It was concluded that green tea drinking inhibited ACF formation in rats, and such effects may be related to the suppression of cell proliferation in the intestinal crypts.     

Mixed tocopherols inhibit azoxymethane-induced aberrant crypt foci in rats

Gamma (gamma) tocopherol, but not alpha (alpha) tocopherol (vitamin E), has previously been reported as an effective inhibitor of cyclooxygenase (COX) enzyme activity. In a pilot study of 17 rats, mixed tocopherols containing more than 50% gamma-tocopherol, added at 0.1% to an AIN-76A diet, produced a significant inhibition (about 55%) of azoxymethane-induced aberrant crypt foci in the colon of rats. Mixed tocopherols also reduced tetradecanoyl phorbol acetate-induced ear inflammation in mice when topically applied.     

Egg yolk proteins suppress azoxymethane-induced aberrant crypt foci formation and cell proliferation in the colon of rats

Dietary proteins can influence colonic carcinogenesis; some proteins have a promotional effect, whereas others exhibit a preventive effect. Dietary egg yolk proteins have been reported to suppress the expression of colon tumors in rats. In this study, we investigated the effect of consumption egg yolk proteins on cell proliferation in a rat model of azoxymethane (AOM)-induced colon cancer. We hypothesize, based on the literature of egg yolk protein actions, that they protect against colon tumor development. Therefore, male F344 rats were fed a purified AIN-93G diet containing either 20% casein (control) or 20% egg yolk proteins for 5 weeks. After 1 week on the experimental diet, the rats were administered weekly subcutaneous injections of saline or AOM for 2 weeks to induce aberrant crypt foci. Rats were administered an intraperitoneal injection of 5-bromo-2′-deoxyuridine 1 hour before being euthanized for examination of DNA synthesis in the colonic mucosa. The contents of the cecum were analyzed for the presence of short-chain fatty acids (SCFAs). In the AOM-injected rats, the yolk protein diet suppressed aberrant crypt foci formation and reduced the proliferative 5-bromo-2′-deoxyuridine–labeling index in the proximal colon when compared with the control diet. A significant increase in cecal SCFAs was observed in the rats that were fed egg yolk proteins. These results indicate that dietary egg yolk proteins have a preventive effect on AOM-induced large bowel carcinogenesis in rats; it exerts this effect by altering cell proliferation through SCFA production. This study suggests that the consumption of egg yolk proteins might be protective against colon carcinogenesis.     

Suppression of intestinal crypt cell proliferation and aberrant crypt foci by dietary quercetin in rats

Quercetin inhibits proliferation of human gastric and colonic cancer cells in vitro by suppressing mitosis and increasing apoptosis. Quercetin might therefore act as an anticarcinogen in the alimentary tract, but previous findings have been inconsistent. We fed rats quercetin at dietary concentrations of 1, 5, 20, and 50 g/kg. At < or = 20 g/kg, we observed a statistically significant reduction in the frequency of crypt cell mitosis in proximal, mid, and distal small intestine and in distal colon, amounting to approximately 40% of control at 1 g/kg. There was no effect on apoptosis. Quercetin metabolites, but not quercetin aglycone, were detected in plasma of rats fed quercetin at 20 and 50 g/kg. In a second experiment, rats were fed quercetin at 1 g/kg after treatment with 1,2-dimethylhydrazine to induce aberrant crypt foci. In dimethylhydrazine-treated and control rats, crypt cell mitosis was suppressed at 48 h and 42 days after injection, and there was a statistically significant reduction in the number of aberrant crypts and larger aberrant crypt foci (> 4 crypts/focus) in the distal colon of treated animals. These findings demonstrate that quercetin can inhibit intestinal crypt cell proliferation in vivo, but the effect diminishes as the level of dietary exposure increases. At low concentrations, dietary quercetin inhibits induction of aberrant crypts by a mechanism that does not involve increased crypt cell apoptosis.     

饮茶对大鼠大肠变性隐窝病灶及大肠肿瘤的影响

以二甲基肼诱发Wistar大鼠大肠癌为模型,研究了绿茶和茶色素(红茶的主要成分)大肠癌的化学预防作用和对大肠肿瘤的影响。结果表明,在第16周2个饮茶组动物的变性隐窝病灶(ACF)形成数比阳性对照组显著减少(P< 0.01);在第32周时阳性对照组100% 发生了肿瘤(平均瘤数为2.6个/只,平均瘤体积为294.7m m 3/瘤)。绿茶组和茶色素组的平均瘤数抑制率分别为47.1% 和43.1% ,平均瘤体积抑制率分别为77.1% 和68.1% 。表明绿茶和茶色素对实验性大肠肿瘤具有预防作用,ACF作为一个有用的中间终点可代替癌发生率进行大肠癌化学预防剂研究     

9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats

We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor gamma were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.     

Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as beta-glucuronidase, beta-glucosidase, beta-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4-6). DMH (0.02 g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P < 0.01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.     

Inhibitory effects of crude salts on the induction and development of colonic aberrant crypt foci in F-344 rats given azoxymethane

The present study was designed to investigate the modifying effects of dietary exposure to NaCl and four kinds of crude salts on the induction and development of aberrant crypt foci in Fischer 344 rats. A total of 57 male rats were divided into five groups at six weeks of age, and all were given weekly injections of azoxymethane (15 mg/kg body wt s.c.) for three weeks. Group 1 was fed a normal diet throughout the experiment as control group. Groups 2, 3, 4, and 5 were fed diets containing 4.4% pure NaCl, 4.4% cooking salt, 4.4% rock salt, and 4.4% beach salt, respectively, from one week before the first azoxymethane dosing. The mean numbers of aberrant crypt foci and aberrant crypts per colon were significantly lower in Groups 3-5 than in Group 1 (p < 0.01). The present results suggest that the other mineral components (e.g., calcium and magnesium) of these crude salts, rather than pure NaCl, may be chemopreventive agents for colonic tumorigenesis.     

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.     

Plant tannins inhibit the induction of aberrant crypt foci and colonic tumors by 1,2-dimethylhydrazine in mice

We have shown that naturally occurring tannins possess antitumor promotion activity in mouse skin. In the present investigation, we studied the ability of a hydrolyzable tannin, gallotannin (GT), and a condensed tannin extracted from red alder (RA) bark to inhibit 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) and tumors in Balb/c mice. In addition, we determined the ability of GT to inhibit the proliferation and to induce apoptosis in a human colon cancer cell line (T-84). Mice were given tannins by intraperitoneal injections, by gavage, or in drinking water before treatment with DMH for 24 weeks. Alternatively, mice were given tannins by intraperitoneal injection or gavage for only 2 weeks before DMH administration, then tannin administration was discontinued and mice were treated with DMH for 24 weeks. The multiplicity, size, and distribution of ACF and tumors were significantly inhibited by GT and RA in the above treatment regimens. The most effective treatments included GT by gavage, RA bark extract by intraperitoneal injection, and either tannin dissolved in drinking water. Extent of inhibition of ACF and tumors was gender independent. In cell culture experiments, GT treatment for three days inhibited the growth of T-84 cells, with a concentration resulting in half-maximal inhibition estimated to be 20 micrograms/ml. The treatment was not cytotoxic to cells at 1-40 micrograms/ml. Interestingly, at 10 micrograms/ml, GT induced apoptosis in T-84 cells as determined by the Hoechst DNA staining technique. Collectively, these findings support a potential role for tannins as chemopreventive agents against colon cancer.     

Carrageenan gel and aberrant crypt foci in the colon of conventional and human flora-associated rats

Carrageenans (CAR) are sulfated polymers from seaweed used as gelling agents in foods. Chemical carcinogen induction of tumors in the colon of rats is enhanced by CAR. We speculated that gut microflora is involved in this effect. We thus studied the initiating and promoting effects of undegraded CAR-kappa (345,000 mol wt) in conventional rats and in germ-free rats associated with a human fecal flora. The initiating effect of CAR was studied by scoring aberrant crypt foci (ACF) in the colon of Fischer 344 rats given CAR (10% in water). The promoting effect of CAR was studied by comparing the multiplicity of ACF (number of crypts/focus) in rats receiving pure water or CAR (0.25% and 2.5% in water) for 100 days, starting 7 days after azoxymethane initiation (1 dose of 20 mg/kg i.p.). Duplicate studies were conducted in conventional rats and in human flora-associated rats maintained in isolators. Results show that CAR did not initiate ACF. In conventional rats, the 2.5% CAR gel promoted the growth of ACF: 2.98 +/- 0.29 and 3.44 +/- 0.48 crypts/ACF in control and treated rats, respectively (p < 0.02). The 0.25% CAR gel did not promote ACF. CAR can thus enhance intestinal tumors in this rat model, but only at a high dose level. In contrast, we did not observe any promoting effect of the administration of the 2.5% CAR gel in human flora-associated rats: 2.81 +/- 0.18 and 2.78 +/- 0.38 crypts/ACF in control and treated rats, respectively (p = 0.80). The specific microflora of rats, but not the human gut flora, might be involved in colon tumor enhancement by CAR.     

Insulin injections promote the growth of aberrant crypt foci in the colon of rats

The main objective of the present study was to test the hypothesis that exogenous insulin would enhance colon carcinogenesis. Thirty‐six female Fischer 344 rats were fed ad libitum a low‐fat rodent chow and given a single azoxymethane injection (20 mg/kg) one week later, they were randomized into two groups. Control rats were given a subcutaneous saline injection, 5 dayslwk, and experimental rats were given Ultralente bovine insulin (20 U/kg). The promoting effect of insulin injections was assessed by the multiplicity (number of crypts) of aberrant crypt foci after 100 days of treatment (72 injections). The rats given insulin ate more and were heavier than controls (215 ± 11 vs. 182 ± 7 g, p < 0.001). Insulin injections also increased the amount of abdominal fat, plasma triglycerides, and in‐sulinemia and decreased blood glucose (all p < 0.05). The number of aberrant crypt foci was the same in both groups, but their multiplicity was significantly increased by the insulin injections (2.8 ± 03 vs. 2.5 ± 0.2 crypt/focus in controls, p = 0.007). In addition, the proportion of sialomucin‐producing foci was higher in insulin‐injected rats than in controls (p = 0.04). These data show that exogenous insulin can promote colon carcinogenesis in rats and suggest that life‐style and diets leading to low blood insulin might protect humans against colorectal cancer.     

Vitamin E supplementation does not alter azoxymethane-induced colonic aberrant crypt foci formation in young or old mice

Vitamin E, part of the body's primary lipid-soluble defense against free radicals and reactive oxygen molecules, has been suggested to reduce the risk for some cancers. However, the role of vitamin E in the etiology and prevention of colon cancer, especially in the highest risk group, the aged, is not clear. Thus, this study was conducted to elucidate the effect of vitamin E supplementation on susceptibility to colon cancer by examining azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation, a surrogate biomarker of colon cancer. Young (3-4 mo) and old (19-20 mo) C57BL/6JNIA mice were fed either a control diet (30 mg dl-alpha-tocopheryl acetate/kg diet) or a vitamin E-supplemented diet (500 mg dl-alpha-tocopheryl acetate/kg diet) for 16 wk. After 6 wk of dietary supplementation, young and old mice were injected with saline or AOM weekly for 5 wk to receive the same total dose of AOM (2.2 mg) and killed 10 wk after the first AOM injection. Vitamin E supplementation had no effect on the number of AOM-induced ACF in young or old mice. In addition, vitamin E supplementation did not have an effect on splenocyte interferon-gamma, interluekin-6 and tumor necrosis factor-alpha levels, natural killer cell killing activity or colonic cell proliferation in young or old mice. Thus, alpha-tocopherol does not seem to affect the initiation and early promotion stages of AOM-induced colon carcinogenesis in young or old mice. Whether vitamin E supplementation might be effective in reducing AOM-induced colon tumors is unclear.     

Feeding soybean resistant protein to rats raises fecal bile acid excretion but counteracts a deoxycholate-caused decrease in colonic aberrant crypt foci.

A high-molecular-weight fraction after removal of water-soluble peptides from proteinase-treated soybean protein isolate (referred to as HMF) was examined for its effect on preneoplastic lesions in the rat colon. For this purpose, male Fisher-344 rats 7 wk old were divided into 8 groups (n = 5), of which 6 groups received 3 injections of azoxymethane (AOM, 15 mg/kg of body weight) for 3 wk once a week, while all were fed HMF or casein diets supplemented with or without deoxycholic acid (DCA) over a period of 4 wk. Two groups of AOM-treated rats were allowed free access to HMF or casein diets without supplemental DCA, respectively, while the others were pair-fed so as to be well matched in their food intake. There were no significant differences in growth parameters among the pair-fed groups. Feeding HMF diets raised fecal lipid and acidic steroid excretions to a greater extent than feeding casein diets, secondary bile acids being conspicuous among acidic steroids in the excreta irrespective of the presence or absence of DCA supplementation. As a result of observation for colonic aberrant crypt foci (ACF), the intake of HMF proved to reverse the reduction of ACF appearance by DCA. This result implies that secondary bile acids are caught and brought out by HMF, or rather its derivative "resistant protein," so as not to keep contact with colonic mucosae.     

Effect of lactobacilli, bifidobacteria and inulin on the formation of aberrant crypt foci in rats

Summary Background Our studies were aimed at investigating the effect of lactic acid producing bacteria (LAB) or inulin, a natural source of non-digestible oligosaccharides derived from chicory, on the induction by carcinogens of aberrant crypt foci (ACF) in the colon, which are considered to be early precursor lesions of neoplasia. Methods Strains of Bifidobacterium longum, Lactobacillus casei and Lactobacillus acidophilus were administered to rats fed a purified high starch diet, under a variety of treatment protocols including daily gavage, via the drinking water and in the diet. The rats were treated with methyl-N-nitrosourea, 1,2-dimethylhydrazine, or azoxymethane (AOM) to induce ACF. Results In general, no consistent significant changes in ACF numbers were detected in these experiments. In one study, the basal diet of the rats was changed to one containing a higher level of fat (corn oil). Under these conditions, a significant decrease in AOM-induced colonic ACF was seen in rats given L. acidophilus or inulin. In a concurrent group of animals fed a low fat diet, no significant decrease in ACF was observed. Conclusions The results indicate that the type of diet fed can influence the detection of protective effects of LAB and oligosaccharides and that against the background of a diet with a level of fat typical of a Western diet, evidence for a protective effect of L. acidophilus and inulin towards colon cancer was obtained Received: 26 July 2001, Accepted: 26 November 2001     

Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings

Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.     

大豆异黄酮对去卵巢大鼠阴道上皮Bcl-2mRNA影响

目的 探讨大豆异黄酮对去卵巢大鼠阴道上皮细胞凋亡及Bcl-2 mRNA表达的影响。方法 Wistar大鼠50只,随机分为假手术组、模型组、雌二醇组、大豆异黄酮高剂量组及低剂量组。采用原位末端标记法及原位杂交方法检测阴道上皮细胞凋亡及Bcl-2 mRNA,并应用图像分析系统进行测定。结果 雌二醇组、大豆异黄酮高、低剂量组均可使去卵巢大鼠阴道重量增加,分别为(0.125±0.024),(0.123±0.020),(0.109±0.022)g,与模型组(0.074±0.046)g比较,差异均有统计学意义(P<0.01);假手术组未见凋亡细胞,其余各组均可见凋亡细胞,大豆异黄酮高、低剂量组凋亡细胞数与雌二醇组比较,差异均有统计学意义(P<0.05);雌二醇组、大豆异黄酮高、低剂量组的Bcl-2 mRNA平均灰度值与模型组比较,差异均有统计学意义(P<0.05),但大豆异黄酮高、低剂量组的Bcl-2 mRNA平均灰度值与雌二醇组比较,差异均无统计学意义。结论 大豆异黄酮可以抑制阴道上皮细胞的凋亡,通过上调Bcl-2 mRNA的表达是其作用途径之一。     

Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats

Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin-type fructan on 1,2-dimethylhydrazine dihydrochloride-induced aberrant crypt foci (ACF) in the rat colon. In addition, the present study investigated the influence of chain length, dietary level (5% or 15%), and duration of feeding (5 or 10 wk) on the following intestinal parameters supposed to be involved in the development of ACF: microflora, short-chain fatty acids, pH, and cell proliferation. A 3-wk pretreatment period with both fructans was included. Feeding the long-chained fructan (5% or 15%) significantly inhibited the numbers of small and total ACF after 5 and 10 wk. The short-chained fructan (15%) inhibited the number of small and total ACF after 5 and 10 wk but significantly increased the numbers of medium and large ACF after 10 wk. In conclusion, the effect on ACF outcome was influenced by the chain length of the fructans.     

Effect of dietary apigenin on colonic ornithine decarboxylase activity, aberrant crypt foci formation, and tumorigenesis in different experimental models

The efficacy of dietary apigenin, a dietary flavonoid, in colon cancer prevention was investigated by evaluating the inhibition of the ornithine decarboxylase (ODC) activity and the formation of aberrant crypt foci (ACF) and by studying the ability of apigenin to block colon carcinogenesis in two mouse models. First, the activity of ODC was measured in colon cancer cells (Caco-2) and in the colon epithelium of CF-1 mice. Apigenin at 10 and 30 muM significantly inhibited the ODC activity of Caco-2 cells by 26% and 57%, respectively. Colonic ODC activity in CF-1 mice was reduced with 0.1% dietary apigenin by 42% compared with the control, but this difference was not statistically significant. Second, ACF formation was evaluated in azoxymethane (AOM)-induced CF-1 mice. Female CF-1 mice at 6 wk of age were i.p. injected with 5 mg/kg body weight (BW) AOM once to induce ACF. ACF formation in CF-1 mice was reduced by 50% (P < 0.05) with 0.1% dietary apigenin fed for 6 wk when compared with the control. Dietary apigenin inhibited ACF only in the distal region of the CF-1 mouse colon. Finally, tumorigenesis studies were conducted using two different mouse models: AOM-induced CF-1 mice and Min mice with mutant adenomatous polyposis coli (APC) gene. Female CF-1 mice at 6 wk of age were i.p. injected with 10 mg/kg BW AOM weekly for 6 (AOM Study I) or 4 (AOM Study II) wk to induce tumors. CF-1 mice were fed diets containing 0.025% or 0.1% apigenin for 23-25 wk. Female Min mice were fed diets for 10 wk beginning at 5 wk of age. In two AOM-treated mouse colon tumor studies 0.025% and 0.1% dietary apigenin modestly reduced tumors in the group fed 0.025% apigenin (25% incidence in comparison with 65% in the controls) in a non-dose response manner. Apigenin failed to inhibit adenoma formation in the Min mouse study. These results suggest that dietary apigenin showed promise in cancer prevention by reducing the ODC activity and ACF formation, however, clear evidence of cancer prevention was not obtained in mouse tumor studies. Further investigation of the potential chemopreventive effect of apigenin in carcinogenesis is warranted.