• Nutritional Sciences
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• v.8 no.4
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• pp.219-225
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• 2005

This study examined the effect of viable bifidobacteria and non-digestible carbohydrates on the cecal pH, colonic neoplastic lesion (aberrant crypt) and proliferating cell nuclear antigen (PCNA) labeling index in carcinogen-treated mts. Animals received s.c. injection of dimethylhydrazine (DMH) (15 mg/kg body weight) twice 3 days apart. Three days after the second carcinogen administration, the treatments were begun. 1he treatments were basal diet (AIN-76) with skim milk (Basal/skim), or the following diets with daily gavage of $10^8$ bifidobacteria: basal (Basal/bifido), $2\%$ fructo-oligosaccharide (FOS/bifido), $2\%$ soybean oligosaccharide (SBO/bifido), $2\%$ wheat bran oligosaccharide (WBO/bifido) and $8.4\%$ wheat bran (WB/bifido). After 4 weeks of treatment, cecal pH was measured using a pH probe. The number of aberrant crypt (AC), aberrant crypt foci (ACF) and crypt multiplicity were enumerated and colonic PCNA labeling index was determined using immunohistochemistry. Cecal pH was significantly reduced in SBO/bifido and FOS/bifido groups compared to control group. However, there were no significant differences in either number of AC or rates of cell proliferation as shown by PCNA labeling index among the groups, although mts fed FOS/bifido reduced the numbers of ACF compared to Basal/skim group. The SBO/bifido group did not reduce the number of ACF or PCNA labeling index. Also, other oligosaccharides did not reduce the risk of colon cancer compared to control group. The concomitant reduction of cecal pH and number of ACF suggest that the combination of bifidobacteria and FOS may reduce the risk of colon cancer.

• Korean Journal of Veterinary Research
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• v.48 no.3
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• pp.337-345
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• 2008

There are accumulating evidences that high levels of dietary iron may play a role in colon carcinogenesis. Elevated iron status has been associated with oxidative stress. Phytic acid (PA) functions as an antioxidant by chelating divalent cations and prevents formation of reactive oxygen species responsible for cell injury and carcinogenesis. The protective effect of PA was investigated on formation of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in iron-overloaded male F344 rats. After acclimation with AIN-93G purified diet (35 ppm Fe, normal control diet) for one week, animals were fed iron-overloaded diet (350 ppm Fe) and PA (0.5% or 2% PA in water) for 8 weeks. Animals received two (1st and 2nd week) injections of AOM (15 mg/kg b.w.) to induce colonic ACF. The colonic mucosa was examined for the total numbers of aberrant crypt (AC) and ACF after staining with methylene blue. The blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. Iron-overloaded diet increased the concentration of iron in liver of the rats. But iron-related parameters in blood were not changed among experimental groups. The numbers of ACF per colon and AC per colon were $178.8{\pm}33.2$ and $448.4{\pm}110.2$ in the iron-overloaded F344 rats. The total AC was significantly increased, compared with normal-diet AOM control group (p < 0.05). The treatments of PA at the dose of 0.5% slightly decreased the number of ACF and AC per colon to $153.6{\pm}29.5$ and $396.3{\pm}107.5$. However, there were no significant differences in the total numbers of ACF and AC between the AOM control group and PA (0.5% or 2%)-treated groups. These results suggest that PA may not affect the formation of ACF or AC induced by AOM in ironoverloaded F344 rats.

• 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.

• Biomedical Science Letters
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• v.16 no.4
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• pp.381-385
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• 2010

Indole-3-carbinol (I3C), one of naturally occurring main components in cauliflower vegetables, is supposed to have a chemopreventive potential in experimental animals and humans. This study was investigated to examine chemopreventive effect of I3C on colon carcinogenesis induced by azoxymethane (AOM) using C57BL/6J mice. Mice were divided into three groups (10 or 9 mice/group). All mice were subcutaneously injected with AOM (5 mg/kg body weight, four times at weekly interval). After AOM treatment, animals of group 1 were fed by AIN-76A pellets as a basal diet. Animals of groups 2 and 3 were given I3C containing diets (100 and 300 ppm in diets, respectively) for 6 weeks until sacrifice. All mice were sacrificed at week 10 and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Total numbers of ACF/colon in group 2 ($10.1{\pm}5.1$) or group 3 ($10.6{\pm}5.3$) were decreased compared to the values of group 1 ($14.4{\pm}10.2$). Among numbers of ACF formation, 5, 7, 8 and 10 ACF in group 2 and 3 were greatly different those of group 1. Total numbers of aberrant crypts (AC)/colon of group 2 ($20.1{\pm}10.1$) or group 3 ($22.0{\pm}10.9$) were decreased compared to the value of group 1 ($33.7{\pm}24.7$). Taken together, it suggests that I3C treatment may retard mouse colon carcinogenesis even after administration of AOM.

• Toxicological Research
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• v.23 no.4
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• pp.321-330
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• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• 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.

• Preventive Nutrition and Food Science
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• v.13 no.3
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• pp.157-165
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• 2008

Cancer-preventive effects of ethanol extract of elm tree root (EEE) were investigated. In the in vitro cytotoxicity assay, colon cancer cells were incubated with a chloroform fraction of EEE (CF-EEE). CF-EEE significantly inhibited the proliferation of cells and induced apoptotic cell death in a dose-dependent manner. For the assessment of chemopreventive efficacy in vivo, male F344 rats were fed with EEE (0.5 or 1%) in diet for 8 weeks, and were subcutaneously injected with 1,2-dimethylhydrazine (DMH) to induce colonic aberrant crypt foci (ACF). EEE (0.5 and 1%) significantly decreased both the numbers of AC (1191.1/colon) and ACF (529.3/colon) induced by DMH. In addition, in the Western blot analysis on the colonic mucosa, administration of EEE triggered expression of caspase-3, a key factor of an apoptotic cascade. These results suggest that extract of elm tree root may have potential chemopreventive principles that lead to apoptosis of cancer cells, and thereby suppress colorectal carcinogenesis during the initiation stage.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6851-6856
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• 2013

In the present report we determined the protective capacity of grapefruit juice (GJ) against molecular and cellular damage in azoxymethane (AOM) treated mice. Animals were daily administered GJ orally (0.8, 4.1, and 8.2 ${\mu}l/g$) for seven weeks, as well as intraperitoneally (ip) injected with AOM twice (weeks 2 and 3 of the assay). Control groups administered with water, with the high dose of GJ, and with AOM injected in weeks 2 and 3 were also included. The results showed a significant, dose-dependent protection of GJ on the number of colon aberrant crypts (AC) induced by AOM. The highest inhibitory effect was reached with the highest tested dose of GJ, decreasing ACF by 51% and 43% at weeks 4 and 7 of the assay. Regarding protein and lipid oxidation we also found a dose-dependent decrease caused with GJ in comparison with the increased levels produced by AOM. Therefore, our results established chemopreventive potential for GJ, and suggested effects related to its antioxidant capacity. Finally, we found that the tested agents induced neither micronuclei increase nor alteration in bone marrow cytotoxicity.