| Popis: |
Background: Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer in high-risk areas in the world, we have investigated the effect of high doses of selenium on gene expression in the esophagus of rats treated with N-nitrosomethylbenzylamine (NMBA). Materials and methods: Esophageal squamous cell carcinoma (ESCC) was induced in Sprague Dawley male rats with NMBA (0.5 mg/kg BW, s.c, three times per week for 5 weeks). Rats in the treated groups were given 0.3, 1.5, and 3 mg/kg body weight sodium selenite for 20 weeks. After euthanizing the rats, esophageal tissue and blood was collected to assess the effects of high dose selenium. Pathological analysis was performed to diagnose preneoplastic lesion in the rat esophagus. Serum malondialdehyde and whole blood glutathione peroxidase activity was measured. Furthermore, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-β, and MGMT were analyzed and compared between groups. Results: In the esophagus of rats treated with NMBA, increasing selenium levels significantly increased the mRNA levels of cyclin D1 and NF-κB p65.The concentrations of cyclin D1 was also significantly increased by high-dose selenium. Moreover, excess dietary selenium had no significant effect on serum MDA but significantly increased GPx activity. Conclusion: The present study proved that high dose of inorganic selenium increases the mRNA levels of cyclin D1 and NF-κB p65 in the esophagus of rats treated with NMBA and may promote carcinogenesis by enhancing oxidative stress, inflammation, and cell proliferation. |
