Selenium (Se) is an essential
micronutrient for humans, acting as a component of the unusual
amino acids,
selenocysteine (Se-Cys) and
selenomethionine (Se-Met). Where Se levels are low, the cell cannot synthesise
selenoproteins, although some
selenoproteins and some tissues are prioritised over others. Characterised functions of known
selenoproteins, include
selenium transport (
selenoprotein P),
antioxidant/redox properties (
glutathione peroxidases (GPxs),
thioredoxin reductases and
selenoprotein P) and anti-inflammatory properties (
selenoprotein S and GPx4). Various forms of Se are consumed as part of a normal diet, or as a dietary supplement. Supplementation of tissue
culture media, animal or human diets with moderate levels of certain Se compounds may protect against the formation of
DNA adducts,
DNA or
chromosome breakage, and chromosome gain or loss. Protective effects have also been shown on
mitochondrial DNA, and on telomere length and function. Some of the effects of Se compounds on gene expression may relate to modulation of DNA methylation or inhibition of
histone deacetylation. Despite a large number of positive effects of
selenium and
selenoproteins in various model systems, there have now been some human clinical trials that have shown adverse effects of Se supplementation, according to various endpoints. Too much Se is as harmful as too little, with animal models showing a "U"-shaped efficacy curve. Current recommended daily allowances differ among countries, but are generally based on the amount of Se necessary to saturate GPx
enzymes. However, increasing evidence suggests that other
enzymes may be more important than GPx for Se action, that optimal levels may depend upon the form of Se being ingested, and vary according to genotype. New paradigms, possibly involving nutrigenomic tools, will be necessary to optimise the forms and levels of Se desirable for maximum protection of
genomic stability in all humans.