Lab Anim Res.  2010 Sep;26(3):293-300.

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

• Kim JH
• Hue JJ
• Kang BS
• Park H
• Nam SY
• Yun YW
• Kim JS
• Jeong JH
• Lee BJ

Abstract

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.

Keyword

Azoxymethane (AOM); dextran sodium sulfate (DSS); colon cancer; selenium; cell proliferation; apoptosis

MeSH Terms

Animals
Apoptosis
Azoxymethane
Blood Cells
Cell Proliferation
Colon
Colonic Neoplasms
Dextrans
Diet
Drinking Water
Hematology
Humans
Incidence
Injections, Intraperitoneal
Liver
Male
Mice
Mice, Inbred ICR
Organothiophosphorus Compounds
Proliferating Cell Nuclear Antigen
Selenium
Sodium
Spectrum Analysis
Sulfates
Azoxymethane
Dextrans
Drinking Water
Organothiophosphorus Compounds
Proliferating Cell Nuclear Antigen
Selenium
Sodium
Sulfates

Figure

• 

  Figure 1. Experimental design for colon carcinogenesis in mice. AOM, azoxymethane; DSS, dextran sodium sulfate.

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  Figure 2. Change in the body weights in mice treated with AOM/DSS and selenium (Se). The body weights of all AOM/DSS treatment groups significantly decreased compared with the body weight of vehicle control group during 2–4th weeks of treatment (P<0.05). AOM: azoxymethane, DSS: dextran sodium sulfate, NSe: normal selenium (0.1 ppm) diet, LSe: low selenium (0.02 ppm) diet, HSe: high selenium (0.5 ppm) diet.

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  Figure 3. Hepatic selenium levels in mice following feeding of different concentrations of dietary selenium. Selenium concentration was determined using an inductively coupled plasma-mass spectroscopy. AOM: azoxymethane, DSS: dextran sodium sulfate, NSe: normal selenium (0.1 ppm) diet, LSe: low selenium (0.02 ppm) diet, HSe: high selenium (0.5 ppm) diet.

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  Figure 4. Effect of selenium on tumor incidence and survival rate of mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS). NSe: normal selenium (0.1 ppm) diet, LSe: low selenium (0.02 ppm) diet, HSe: high selenium (0.5 ppm) diet.

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  Figure 5. Immunohistochemistry on proliferating cell nuclear antigen (PCNA) in the colon of mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) and selenium (Se). The PCNA-positive cells were greatly increased by treatment with AOM/DSS, which were markedly reduced by coadministration of a high concentration (0.5 ppm) of selenium (Se). (A) Vehicle control. (B) AOM/DSS+normal Se (0.1 ppm) diet. (C) AOM/DSS+low Se (0.02 ppm) diet. (D) AOM/DSS+ high Se (0.5 ppm) diet. ×100.

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  Figure 6. TUNEL assay for apoptotic nuclei in distal colon sections of mice treated with azoxymethane/dextran sodium sulfate (AOM/DSS) and selenium (Se). The TUNEL-positive cells were increased by treatment with AOM/DSS, which were further enhanced by co-administration of Se in a concentration-dependent manner. (A) Vehicle control. (B) AOM/DSS+normal Se (0.1 ppm) diet. (C) AOM/DSS+low Se (0.02 ppm) diet. (D) AOM/DSS+high Se (0.5 ppm) diet. ×100.

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