The current study was designed to investigate the effect of Red ginseng extract on development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week old animals received subcutaneous injections of DMH (30 mg/kg body weight) four times, for a period of two weeks in order to induce ACF. The animals were divided into groups fed a diet containing red ginseng extract at three different doses (0.5, 1.0, and 2.0%), 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 formation was observed in animals in the DMH-treated group. Four-time treatment with DMH induced mean 265.8±48.3 ACF/colon composed of a total of 608.8±110.9 aberrant crypts AC/colon. The numbers of ACF and AC induced by DMH were decreased to 204.4±29.3 and 464.7±70.3 by treatment with 0.5% red ginseng extract. In addition, the number of large ACF (≥4 AC/ACF) was suppressed from 39.9±10.6 ACF/colon in control to 28.5±5.3 ACF/colon in 0.5% red ginseng extract. These results suggested that red ginseng extract exerted a chemopreventive effect on DMH-induced colon cancer by inhibiting development of ACF and AC in F344 rats.

Iron catalyzes the production of free radicals, which can be related to a variety of pathological events, such as cancer and aging. The effect of dietary iron was investigated on formation of colonic aberrant crypt foci (ACF) induced by azoxymethane in male F344 rats. Animals were fed three different diets, including iron-deficient (3 ppm Fe), iron-normal (35 ppm Fe), and iron-overloaded (350 ppm Fe) diets for eight weeks. During the first and second weeks of the experiment, animals received two subcutaneous injections of azoxymethane (AOM, 15 mg/kg body weight) to induce ACF. After staining with methylene blue, the total numbers of ACF and aberrant crypts (AC) were counted on the colonic mucosa. Analysis of blood and serum was performed using a blood cell differential counter and an automatic serum analyzer. Iron-deficient diets induced a significant decrease in red blood cell counts and the values of hemoglobin concentration, hematocrit, mean corpuscular hemoglobin, and mean corpuscular volume, while an iron-overloaded diet did not affect these values. The iron-overloaded diet induced an increase in deposits of iron in the liver of rats, as determined by the ICP method and Perl’s staining. The numbers of ACF per colon showed a slight increase in iron-overloaded or iron-deficient rats, without statistical significance, compared to iron-normal rats. The number of total AC per colon in iron-overloaded rats was significantly higher than that in iron-normal rats (p<0.05). The number of large ACF (≥ 4 AC per ACF) in iron-overloaded rats was also significantly higher than that in iron-normal rats (p<0.05). These results suggest that dietary iron intake may play an important role in colon carcinogenesis in humans and animals.

A level of dietary iron may play a role in colon carcinogenesis. The effect of dietary iron on colon carcinogenesis was investigated in male ICR mice. Five-week old mice were acclimated for one week and fed on iron-normal diet (35 ppm Fe), iron-deficient diet (3 ppm), or iron-overloaded diet (350 ppm Fe) for 8 weeks. Animals received three (0-2^nd weeks after starting experiment) injections of azoxymethane (AOM; 10 mg/kg b.w.) to induce colonic aberrant crypt foci (ACF). There were five experimental groups including normal control without AOM, AOM+iron-normal diet (AOM+NFe), AOM+iron-deficient (AOM+LFe), AOM+ironoverloaded diet (AOM+HFe) groups. The total numbers of ACF and aberrant crypt (AC) were measured in the colonic mucosa after staining with methylene blue. The blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. The hepatic iron levels were significantly dependent on the presence of iron in the diets. Iron-deficient diet significantly decreased the several hematological values. The values of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) were also significantly decreased in iron-overloaded or iron-deficient diet groups, compared with normal iron diet group. Dietary iron-deficiency decreased the numbers of ACF (64.9) and AC (79.8) per colon by 20.6 and 21.8%, respectively, compared with AOM+NFe group (72.4 ACF/colon and 90.3 AC/colon). However, ironoverloaded diet increased ACF (82.9) and AC (96.0) induction by AOM, compared with normal iron diet. These results suggest that dietary iron can affect the colon carcinogenesis in the animal model of mice.

Phytic acid (PA) (Inositol hexaphosphate, IP6) 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 (1st and 2nd 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 ± 22.3 ACF/colon and 336.6 ± 55.1 AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dosedependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were 124.4 ± 28.5 and 302.7 ± 67.3, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 109 ± 18.1 and 254.8 ± 50.6, respectively (p < 0.01). Especially, 2% PA significantly reduced the number of large ACF ( ≥ 4 AC/ ACF) from 26.8 ± 6.2 ACF/colon to 15 ± 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.

Phytic acid (PA) is a naturallu 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. We investigated the preventive effect of PA on the formation of colonic aberrant crypt foci (ACF), a preneoplastic lesion, induced by azoxymethane (AOM). After acclimation for one week, six-week old male ICR mice were fed on the AIN-93G purified diet and PA (0.5% or 2% PA in water) for 8 weeks. The animals were treated with azoxymethane (AOM, 10 mg/kg b.w.) three times (0, 1, and 2 weeks) to induce colonic aberrant crypt foci (ACF). After sacrifice, the total numbers of aberrant crypts (AC) and ACF in colonic mucosa were counted after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM treatment without PA induced the total numbers of 85.7 ± 12.9 and 115.2 ± 19.9, respectively. PA at the dose of 2% AC/colon by PA at the dose of 0.5% were 73.4 ± 12.9 and 115.2 ± 19.9, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 56.5 ± 14.6 and 95.4 ± 17.2, respectively (p＜0.01). PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. Theses findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in ICR mice.