Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon

Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086mg Se/kg) or a selenium-adequate (0.15mg Se/kg) diet. After 6wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status. Male C57BL/6J mice (3–4 wk of age) from Charles River (Sulzfeld, Germany) were randomly assigned to the selenium-deficient or selenium-adequate group (12 mice per group) with free access to food and water. The selenium-adequate diet (Se-adeq) was produced by mixing selenomethionine (Acros, Geel, Belgium) into the selenium-deficient diet (Se-def; No. C1045 with 50% carbohydrates, 17% protein, 5% fat, 4% fibre, and mixture of micronutrients; Altromin, Lage, Germany) containing 0.086mg Se/kg (Riese et al., Endocrinology 2006) to yield a selenium content of 0.15 mg/kg corresponding to the dietary reference intake for mice. Diets were fed as powder for 6wk until mice were killed in the non-fasted state. Animals were anesthetized with isofluran and blood was withdrawn from the retro-orbital plexus. Anesthetized animals were killed by cervical dislocation. Plasma and tissues freeze clamped in liquid nitrogen were stored at -80C.