title: Effects of selenium on colon carcinogenesis induced by azoxymethane and dextran sodium sulfate in mouse model with high-iron diet.
abstract: 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.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jun-Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin-Joo
authors.initials: JJ
authors.lastname: Hue
authors.forename: Bong Su
authors.initials: BS
authors.lastname: Kang
authors.forename: Hyunji
authors.initials: H
authors.lastname: Park
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Nam
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Lee