Selenium is an essential micronutrient which functions as an essential constituent of selenoproteins. The selenoproteins play an important role in the body’s defense from free radicals associated with chronic diseases such as cancer. The effect of selenium on colon carcinogenesis was investigated using an experimental animal model. Five-week old ICR mice were acclimated for one week, and fed on the Fe-overloaded diet (450 ppm) with different Se diets (0.02, 0.1 or 0.5 ppm) for 12 weeks. Animals were injected intraperitoneally with azoxymethane (AOM, 10 mg/㎏ B.W. weekly for 3 weeks), followed by 2% dextran sodium sulfate (DSS) in the drinking water for a week. There were three experimental groups including low Se group (Lse), medium (normal standard diet for mice) Se (MSe), and high Se (HSe). The numbers of aberrant crypt foci (ACF) and aberrant crypt (AC) were measured in the colonic mucosa. The iron and selenium concentrations in liver was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined in the liver and colon. TUNEL assay for cell apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell proliferation were performed. Immunohistochemical staining of β-catenin was also performed in mucous tissue of colon. The dietary Se decreased the numbers of ACF/㎠ and AC/㎠ in a dose-dependent manner. HSe diet significantly decreased the numbers of AC/㎠, compared with LSe diet (p<0.05). The tumor incidence rate in low Se diet group was 5% higher than medium Se diet group and 20% higher than high Se diet group. The activities of GPx in the liver and colon were dependent on the content of dietary selenium. Apoptosis-positive cells were also increased by dietary Se in a dose-dependent manner. PCNA-positive staining was weak in high Se group. β-catenin stained area was increased in low Se group while it was decreased in high Se group. These findings indicate that dietary selenium exert a protecting effect on colon cancer by inhibiting the development of ACF/AC, increasing GPX and apoptosis, and decreasing cell proliferation and expression of β-catenin in mice.

Selenium (Se) obtained from dietary sources is an essential micronutrient for normal body function and it functions as an essential constituent of selenoproteins. We investigated the influence of Se on the formation of colonic aberrant crpyt foci (ACF) and tumor formation induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in male ICR mice. Five-week old ICR mice were acclimated for one week and fed on the low iron diet (LFe, 4.5 ppm) and different Se diet [Lse (0.02 ppm), Normal Se (0.1 ppm), HSe (0.5 ppm)] for 12 weeks. Animals received intraperitoneal injections of AOM (10㎎/㎏ B.W. in saline weekly for 3 weeks), followed by 2% DSS (molecular weight 36,000～50,000) in the drinking water for a week. There were five experimental groups, including a normal control group, AOM/DSS, LFe+AOM/DSS, LFe+AOM/DSS+LSe, LFe+AOM/DSS+HSe. After sacrifice of animals, the total numbers of AC and ACF were measured in the colonic mucosa. The number of mice bearing tumors was expressed as tumor incidence rate. The iron and selenium liver concentration was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation. In addition, immunohistochemistry of β-catenin was also performed on the mucous membrane tissue of colon. In AOM/DSS-induced colon carcinogenesis animal model, LFe diet decreased the number of 2.95±2.5 ACF/cm2 to 1.85±1.1 ACF/cm2 but it increased the total number of 5.06±4.2 AC/cm2 to 6.19±4.8 AC/cm2 compared with normal iron diet. In the iron-deficient mice, selenium did not affect the either the number of ACF or AC. The tumor incidence rate was higher in LFe diet groups than in normal iron diet group and high selenium diet weakly reduced the tumor incidence. Low selenium diet decreased the activity of GPx in the liver and colon. Apoptotic positive cells were decreased in the low selenium diet group. In addition, on the β-catenin staining, positive cells were increased in the low selenium diet group while they were decreased in the high selenium diet group. These findings indicate that the dietary levels of selenium was not highly enough to exhibit a significant protection against colon carcinogenesis in the iron-deficient mice. However, our results also indicate that dietary selenium might exert a protecting effect against colon cancer by increasing GPx activity and apoptosis and by inhibiting cell proliferation and β-catenin over-expression.