Toxicol Res.  2012 Mar;28(1):39-49.

Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron

• Park H
• Kang BS
• Kim DY
• Yoon JS
• Jeong JH
• Nam SY
• Yun YW
• Kim JS
• Lee BJ

Abstract

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). Six-week 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 (> or = 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.

Keyword

Colon carcinogenesis; Zinc; Iron overload; Aberrant crypt foci (ACF); Mouse

MeSH Terms

Aberrant Crypt Foci
Animals
Apoptosis
Azoxymethane
beta Catenin
Colon
Cytosol
Dextrans
Diet
Dietary Supplements
Drinking Water
Ferrocyanides
Immunohistochemistry
Injections, Intraperitoneal
Iron
Iron Overload
Iron, Dietary
Liver
Mice
Mice, Inbred ICR
Mucous Membrane
Prussian Blue Reaction
Sodium
Sulfates
Superoxide Dismutase
Zinc
Azoxymethane
Dextrans
Drinking Water
Ferrocyanides
Iron
Iron, Dietary
Sodium
Sulfates
Superoxide Dismutase
Zinc
beta Catenin