• Journal of Food Hygiene and Safety
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• v.23 no.3
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• pp.264-270
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• 2008

Phytic acid(PA) (Inositol hexaphosphate, $IP_6$) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA(0.5% or 2% PA in water) for 8 weeks. The animals received two ($1^{st}\;and\;2^{nd}$ week) injections of azoxymethane(AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci(ACF). After sacrifice, the total numbers of aberrant crypts(AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of $142.3{\pm}22.3$ ACF/colon and $336.6{\pm}55.1$ AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were $124.4{\pm}28.5\;and\;302.7{\pm}67.3$, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to $109{\pm}18.1\;and\;254.8{\pm}50.6$, respectively(p<0.01). Especially, 2% PA significantly reduced the number of large ACF(${\geq}4$ AC/ACF) from $26.8{\pm}6.2$ ACF/colon to $15{\pm}6.7$ ACF/colon(p<0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

• Journal of Microbiology
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• v.38 no.3
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• pp.169-175
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• 2000

Epidemiological and experimental studies provide evidences that diet and intestinal microflora play an important role in colon carcinogenesis. In recent years, it has been suggested that lactic acid bacteria (LAB) used to ferment dairy products have an inhibitory effect on the colon cancer. This study was designed to determine the effect of Bifidobacterium longum HY8001 (Bif) and Lactobacillus acidophilus HY2104(Lac) of Korean origin on azoxymethane (AOM)-induced colonic preneoplastic lesions such as aberrant crypt foci(ACF) formation and cecal pH. At five weeks of age, Spraque-Dawley rats were divided at random into four (AOM alone, Bif, ,Lac, and Bif+Lac) groups. Animals were weighed weekly and oral administration of LAB cultures were performed daily until the termination of the study. Two weeks later, all animals were given a subcutaneous injection of AOM dissolved in normal saline at a dose of 15 mg/kg of body weight once per week for 2 weeks. All rats were necropsied 7 weeks after the last AOM injection , and the ACF were visualize under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons. The total number of aberrant crypt in Bif, Lac, and Bif+Lac groups were significantly lower than that of the AOM alone group and the percentage of inhibitions weas 35.0, 45.6%, respectively. Significant inhibition (p<0.001) in the total number of ACF was also observed in LAB treated groups (Bif , Lac, and Bif+Lac group by 3003, 38.6, and 41.2%, respectively). Furthermore, cecal pH appeared to significantly decrease by LAB administration. The results of present study provide some evidences for potential colon tumor-inhibitory properties of lactic cultures and fermented dairy products.

• Food Science and Biotechnology
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• v.15 no.6
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• pp.942-947
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• 2006

The effect of oat bran extracts on the formation of aberrant crypt foci (ACF) in the colon induced by 1,2-dimethylhydrazine (DMH) was studied in F344 male rats. Extracts were prepared using various combinations of temperature (40, 45, 50, 55, or 60$^{\circ}C:\;X_1$), ethanol concentration (0,5, 10, 15, or 20%: $X_2$), and pH (5, 6, 7, 8, or 9: $X_3$). Among the various extracts tested, one ethanol extract (EE; $45^{\circ}C$, 15% ethanol at pH 6) and one water extract (WE; $50^{\circ}C$ at pH 5) were selected based on their in vitro antitumor activity. The animals were fed with basal diet alone or basal diet supplemented with 0.25 or 0.5% of EE or WE for 6 weeks. During the initial 2 weeks of the 6-week test period, the rats were subcutaneously injected with DMH (30 mg/kg) 4 times for the induction of ACF. DMH induced an average of 322.7 and 142.9 aberrant crypts (AC) and ACF, respectively. A low dose (0.25%) of EE (containing 38.3% ${\beta}$-glucan) and WE (containing 22.8% ${\beta}$-glucan) greatly reduced the numbers of DMH-induced AC and ACF. Significantly, ACF consisting of more than 3 AC were reduced by half in which the effect of EE, containing a higher concentration of ${\beta}$-glucan, was superior to that of WE. These results demonstrate that oat bran extracts may confer protection against colon carcinogenesis.

• International Journal of Internet, Broadcasting and Communication
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• v.12 no.2
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• pp.98-112
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• 2020

There is a strong connection between the diet rich in antioxidants and the decreased incidence of inflammatory bowel disease and cancerous diseases. Diets that are rich in anti-oxidants particularly include fruits and vegetables containing the high amounts of vitamin A-E, carotenoids, and minerals. The supercritical heat-treated radish extracts of the research result had an inhibitory effect on the development of aberrant crypt foci (ACF), namely, preneoplastic lesions having a potential to become cancer cells and reduced the number of the aberrant crypt foci (ACF) consisting of four or more aberrant crypts (AC) having high risk to become tumors by about half. The supercritical heat-treated radish extracts can reduce the incidence of preneoplastic lesions having a high risk of developing cancer by about 28 %. DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. Supercritical heat-treated radish extracts, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, supercritical heat-treated radish extracts treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways, and prevented the apoptosis of colon. Moreover, supercritical heat-treated radish extracts administration significantly led to the up-regulation of anti-oxidant enzyme including SOD and Catalase.

• Toxicological Research
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• v.28 no.1
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• pp.39-49
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• 2012

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of ${\beta}$-catenin was also performed on the mucous membrane of colon. The number of large ACF (${\geq}4$ AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.55-61
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• 2008

We investigated the combinatorial effects of different doses of dietary soy isoflavones (SI) and fructooligosaccharide (FOS) in a rat model of colon cancer. We hypothesized that increased bioavailability of SI metabolites due to dietary FOS may increase production of bioactive equol and affect colon carcinogenesis in a dose-dependent manner. Sprague-Dawley male rats were injected with 12-dimethylhydrazine (DMH) and were providec experimental diets that contained 0, 10, 50, 150, or 500 mg SI per kg of diet and 6% FOS for 12 weeks. The number of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) in colonic tissues were significantly decreased in the 6% FOS-fed groups compared to the control group. Gut transit time and fecal pH were significantly lower, and fecal concentrations of bifidobacteria were increased with 6% FOS. However, dietary SI supplementation in combination with 6% dietary FOS did not affect ACF formation or COX-2 expression. Plasma equol concentrations were dose-dependently increased by supplementation of SI up to 500 mg/kg of diet. In conclusion, SI supplementation up to 500 mg/kg of diet appeared to have no additive beneficial effects in rats with chemically-induced colon cancer that were fed 6% FOS, although plasma equol was dose-dependently increased.

• Journal of Microbiology and Biotechnology
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• v.9 no.3
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• pp.368-370
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• 1999

The protective role of Bifidobacterium spp. (B. breve K-110, B. breve K-111, and B. infantis K-525) isolated from the fecal samples of healthy Koreans was investigated on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci(ACF) formation in mouse colon. In mice fed normal diet with DMH treatment, an average of 68.5 ACF/colon was formed, whereas in mice administered with B. breve K-110, B. breve K-111, and B. infantis K-525, the numbers of DMH-induced ACF decreased to 7.2, 10.9, and 6.6 ACF/ colon, respectively. The mean number of crypts/focus was not significantly altered. Fecal harmful enzymes, such as β-glucuronidase, tryptophanase, and urease, were effectively inhibited during the administration of these bifidobacteria to mice. These results suggest that bifidobacteria could prevent colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7561-7566
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• 2015

Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary diseases. However, its dietary effect on chemoprevention of colon cancer has never been studied. The present study was to evaluate the protective effects of dietary ZJ on colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between was administered to induce colitis-associated colon cancer. ZJ fruit was supplemented in feed as 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation thereby decreasing the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation delayed the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leucocytes, main regulators of cancer inflammation. Therefore, dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

• Korean Journal of Veterinary Research
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• v.52 no.2
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• Journal of Food Hygiene and Safety
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• v.25 no.3
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• pp.269-277
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• 2010

Selenium is an essential micronutrient for normal body function and functions as an essential constituent of selenoproteins. This study was carried out to investigate effect of selenium on the formation of colonic aberrant crypt foci (ACF) and tumor formation in a mouse model. Five-week old ICR mice were acclimated for one week and fed different selenium diet (0.02, 0.1, and 0.5 ppm) for 12 weeks. Animals received three intraperitoneal injections of azoxymethane (10 mg/kg B.W. in saline for 3 weeks), followed by 2% dextran sodium sulfate in the drinking water for a week. There were four experimental groups, including a normal control group and three different selenium levels groups. After sacrifice, the total numbers of aberrant crypt (AC) and ACF were measured in the colonic mucosa after methylene blue staining. The number of tumors was noted for tumor incidence. Liver selenium concentration was measured using ICP-AES method. Gutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL assay and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation, respectively. Immunohistochemistry of $\beta$-catenin was also performed on the mucous membrane tissue of colon. The activity of GPx in the liver and colon was decreased in the selenium-deficient diet group while it was increased in the selenium-overloaded diet group. Apoptotic positive cells were increased in the selenium-overloaded diet group but decreased in the selenium-deficient diet group. PCNA staining area was decreased in the selenium-overloaded diet group. In addition, the $\beta$-catenin protein level in the selenium-deficient diet group was increased but decreased in the selenium-overloaded diet group. These results indicate that dietary selenium might exert a modulating effect on colon cancer by inhibiting the development of ACF and colon tumor formation in this mouse model.