Effects of Selenium on Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in Mouse Model with High-Iron Diet / 한국실험동물학회지

Selenium (Se) is known to prevent several cancers while the relationship between high iron and the risk of colorectal cancer is controversial. To investigate the effects of Se in colon carcinogenesis, we subjected three different levels of Se and high-iron diet to a mouse model of colon cancer in which animals were treated with three azoxymethane (AOM) injections followed by dextran sodium sulfate (DSS) administration. There were five experimental groups including vehicle group [normal-Fe (NFe, 45 ppm)+medium-Se (MSe, 0.1 ppm)], positive control group (AOM/DSS+NFe+MSe), AOM/DSS+high-Fe (HFe, 450 ppm)+low-Se (LSe, 0.02 ppm), AOM/DSS+HFe+MSe, and AOM/DSS+HFe+high-Se (HSe, 0.5 ppm). The animals were fed on the three different Se diets for 24 weeks. The incidence of colon tumor in the high-Se diet group (AOM/DSS+HFe+HSe) showed 19.4% lower than positive control group, 5.9% lower than AOM/DSS+HFe+MSe diet group, and 11.1% lower than AOM/DSS+HFe+LSe group. The tumor multiplicity was significantly higher in the low-Se diet group (AOM/DSS+HFe+LSe) compare to all other AOM/DSS treated groups. In the high-Se diet group, the activity of hepatic GPx was comparable to that of positive control group, and significantly higher than those of low-Se or medium-Se diet groups. Expression level of hepatic GPx-1 showed similar results. Hepatic malondialdehyde (MDA) level (indicator of oxidative stress) in the low-Se diet group showed the highest compared to the other groups, and it was significantly higher than positive control group. In the high-Se diet group the level of MDA in the liver was significantly lower than all other AOM/DSS treated groups. High-Se diet group showed significantly lower proliferative index than low-Se and medium-Se groups. The apoptotic indices in low-Se group and medium-Se group were significantly lower than positive control group. However, apoptotic index of high-Se diet group was significantly higher than all other AOM/DSS treated groups. These findings suggest that dietary Se supplement may have protective effect against colon cancer by decreasing proliferation, increasing apoptosis of tumor cells, and reducing oxidative stress in mice with high iron diet.

Modifying Effect of Indole-3-carbinol on the Rat Colon Carcinogenesis / 한국실험동물학회지

Indole-3-carbinol (I3C) found in various cruciferous vegetables has been shown to exert anti-carcinogenic activity in several target organs. Our study was conducted to assess the modifying effect of I3C on the development of colon tumor induced by azoxymethane (AOM). Eighty-seven male F344 rats were divided into 5 groups and were treated with AOM followed by I3C 100 or 300 ppm, AOM alone, I3C alone, and non-treatment, respectively. The animals were subcutaneously injected with AOM. Then diet containing I3C were fed to the rats for 37 weeks. All rats were sacrificed at 40 weeks. Liver and kidney weights of rats treated with I3C at doses of 100 or 300 ppm were significantly increased compared to those of the control group. Colonic tumor incidence and multiplicity of rats treated with I3C at doses of 100 and 300 ppm were not significant compared to those of AOM alone group. In the pathological examination, most of tumors were classified with adenoma and adenocarcinoma in the small and large intestine. These results demonstrated that I3C may have not chemopreventive effect on the rat colon carcinogenesis.

Dietary Selenium Supplement Prevents Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in ICR Mice / 한국실험동물학회지

The role of selenium (Se) in modulating colon carcinogenesis induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) was investigated in mice. Five-week old ICR mice were fed on diets containing different concentrations (0.02, 0.1 or 0.5 ppm) of Se for 24 weeks. Animals received three (0-2nd weeks) intraperitoneal injections of AOM (10 mg/kg body weight), followed by 2% DSS with drinking water for additional 1 week. There were 4 experimental groups including vehicle control group, positive control group given AOM/DSS with AIN-93G normal diet containing 0.1% Se (NSe), a low (0.02 ppm)-Se diet group (LSe) and a high (0.5 ppm)-Se diet group (HSe). Hematology was analyzed with a blood cell differential counter. Liver Se was analyzed by inductively coupled plasma-mass spectroscopy. Cell proliferation and apoptosis were determined by using proliferating cell nuclear antigen (PCNA) for proliferative activity and apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. HSe group showed a low incidence of colonic tumor (64.7%), compared with the NSe positive control (75%) and LSe (77.8%) groups. In contrast, HSe group exhibited lower rate of PCNA-positive cells (39.3+/-6.9%) than positive control (64.3+/-0.3%) and LSe (57.3+/-2.9%) groups. In addition, apoptotic index of HSe group was higher than those of positive control and LSe groups. These results indicate that Se is a chemopreventive agent for colon carcinogenesis induced by AOM+DSS in male ICR mice.

Dietary Selenium Supplement Prevents Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in ICR Mice / 한국실험동물학회지

The role of selenium (Se) in modulating colon carcinogenesis induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) was investigated in mice. Five-week old ICR mice were fed on diets containing different concentrations (0.02, 0.1 or 0.5 ppm) of Se for 24 weeks. Animals received three (0-2nd weeks) intraperitoneal injections of AOM (10 mg/kg body weight), followed by 2% DSS with drinking water for additional 1 week. There were 4 experimental groups including vehicle control group, positive control group given AOM/DSS with AIN-93G normal diet containing 0.1% Se (NSe), a low (0.02 ppm)-Se diet group (LSe) and a high (0.5 ppm)-Se diet group (HSe). Hematology was analyzed with a blood cell differential counter. Liver Se was analyzed by inductively coupled plasma-mass spectroscopy. Cell proliferation and apoptosis were determined by using proliferating cell nuclear antigen (PCNA) for proliferative activity and apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. HSe group showed a low incidence of colonic tumor (64.7%), compared with the NSe positive control (75%) and LSe (77.8%) groups. In contrast, HSe group exhibited lower rate of PCNA-positive cells (39.3+/-6.9%) than positive control (64.3+/-0.3%) and LSe (57.3+/-2.9%) groups. In addition, apoptotic index of HSe group was higher than those of positive control and LSe groups. These results indicate that Se is a chemopreventive agent for colon carcinogenesis induced by AOM+DSS in male ICR mice.