• 한국식품위생안전성학회지
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• 제23권3호
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• pp.264-270
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• 2008

대장암은 국민경제 수준의 향상과 식생활의 서구화에 따라 급격하게 증가하여, 등록환자 기준으로 2005년 현재 위암에 이어 두 번째로 많은 상태이다. 특히 육류에 많이 함유된 철분 및 지방의 과다섭취가 주요원인으로 여겨지고 있다. Phytic acid(PA) (Inositol hexaphosphate, IP6)는 식물의 박류, 콩류 등에 약 0.1-5% 농도로 존재하며, 포유류의 세포에서도 존재한다. PA는 금속이온과 결합하는 성질을 갖고 있어서, hydroxyl radical과 같은 활성산소종의 형성을 억제하여 항산화 작용을 나타낸다. 본 연구에서는 PA가 대장암 발생의 전암병변인 aberrant crypt faci(ACF) 의 발생을 억제하는지를 조사하고자 수컷 F344 랫드를 사용하였다. Azoxymethane(AOM)을 실험시작 1주 및 2번째 주에 투여함으로 ACF를 유발하였고, 실험기간은 8주로서 AIN-93G 사료급여와 동시에 음수로서 0.5%와 2% PA를 급여하였다. 부검 후, 혈액검사와 대장암 발생의 초기단계인 ACF를 측정하였다. 결과로서 AOM 투여 대조군과 비교해 볼 때 PA의 농도가 증가함에 따라 ACF와 aberrant crypt(AC)의 수가 감소하였고, 2% PA는 유의적으로 ACF와 AC의 수를 감소시켰으며, 더욱이 4개 이상 AC를 갖는 ACF의 수를 유의적으로 감소시켰다. 또한 혈액 생화학적 수치에서 어느 정도 유의적 변화가 나타났지만 정상범위내에서의 변화로서 인정될 수 있을 것이다. 본 실험에서 이러한 결과는 phytic acid가 대장암 발생과정에 전암병변의 형성을 억제함으로서 최종 대장암발생에 억제효과를 나타낼 수 있을 것이라 사료된다.

• Journal of Microbiology
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• 제38권3호
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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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• 제15권6호
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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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• 제12권2호
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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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• 제28권1호
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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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• 제2권2호
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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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• 제9권3호
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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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• 제16권17호
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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.

• 대한수의학회지
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• 제52권2호
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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.

• 한국식품위생안전성학회지
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• 제25권3호
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• pp.269-277
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• 2010

본 연구에서는 azoxymethane (AOM)과 dextran sodium sulfate (DSS)로 유도된 대장 발암과정에 대한 셀레늄의 방어 효과를 조사하였다. 셀레늄 결핍(0.02 ppm Se), 정상(0.1 ppm Se), 과다(0.5 ppm Se)사료를 12주간 식이로 급여하여 혈액검사와 대장암 발생의 초기단계인 aberrant crypt foci (ACF)수를 측정했으며, 암 발생율을 조사하였다. ICP-AES를 사용하여 간의 셀레늄 농도를 측정하였으며, 또한 셀레늄포함 항산화효소인 glutathione peroxidase (GPx) 활성을 알아보았다. 또한 TUNEL assay와 PCNA, $\beta$-catenin에 대한 면역조직 염색을 수행하였다. ACF 수 및 종양 발생률에 있어서, 셀레늄과다사료를 급여한 군이 정상셀레늄사료를 급여한 군보다 낮았으며, 셀레늄결핍사료를 급여한 군은 오히려 ACF 수 및 종양 발생률이 높았다. GPx 활성은 셀레늄의 섭취가 과다한 군에서 높게 나타났으며, 이 때, TUNEL에서 apoptotic positive cell이 증가하는 것을 확인했다. 또한 셀레늄의 섭취가 과다한 군에서 PCNA와 $\beta$-catenin의 발현이 감소됨을 볼 수 있었다. 본 마우스 모델실험에서 셀레늄은 여러 기전에 의해 대장암 발생을 억제할 수 있을 것으로 사료된다.