Selenium is an essential micronutrient for human and animals. The function of selenium has been mainly attributed to its presence in selenoproteins. Selenium was first proposed as an antitumorigenic trace element in the late 1960s, a decade later than it was identified as a nutritional essential, based on ecological associations of cancer mortality rates and crop selenium contents in the United States. Since then, a large body of scientific evidence indicated that selenium can play a role in cancer prevention. This is supported by an extraordinarily consistent body of discoveries from studies with animal tumor and cell culture models, and by some, but not all epidemiologic studies. Both inorganic and organic selenium-compounds can be antitumorigenic at doses greater than those required to support the maximal expression of the selenoenzymes that are generally regarded as discharging the nutritional effects of the element. The evidence for selenium as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastic-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with selenium have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest selenium status. As the level of selenium that appears to be required for optimal effect is higher than that previously understood to be required to maximize the activity of selenoenzymes, the questions has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between selenium, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer selenium metabolites such as methyl selenol formed from gama-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and selenium-enriched yeast or garlic that have anti-cancer effects. Several cancer preventive mechanisms have been described and it is likely that selenium acts through multiple pathways including inhibition of cell proliferation, induction of cell apoptosis, inhibition of angiogenesis, the anti-oxidative, and anti-inflammatory effects mediated through activity of selenoenzymes. Genetic variation in selenoenzymes may modify the potential chemopreventive effect of selenium and need to be further investigated. Current primary and secondary prevention trials of selenium are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial relating to prostate cancer. It will be important to further evaluate the potential chemopreventive effect of selenium.

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Selenium (Se) is an essential trace element in human nutrition. In this review, contents, chemical species and nutritional availability of Se in foods and Se intake in Japanese are discussed. Most fish meats showed high Se values (> 0.3 μg/g) . Se contents in cereal and beans are varied dependently to soil Se contents; high Se contents are observed in wheat and soybeans grown on a central area of North American Continent. Since Japan imports a large amount of wheat and soybean, most of bread, pasta and natto sold in Japan show high Se contents (> 0.1 μg/g) . In addition, north American cereals and beans are used as materials for feed of livestock, meats and eggs also show high Se (> 0.1 μg/g) in Japan. Se intake of Japanese is estimated to be about 100 μg/d which is comparatively high among the world. Se species in cereals and beans with a normal range of Se (< 0.5 μg/g) and that in Se-enriched yeast are protein-bound selenomethionine, while a part of Se species in fish meat is believed to be selenocysteine. Most Se-enriched vegetables contains Se-methylselenocysteine as a major Se species and a part of Se-enriched vegetables contain selenohomolanthionine and γ-glutamyl-Se-methylselenocysteine. Nutritional availability of Se in foods is able to be estimated by a slope ratio analysis. The availability of Se in Se-enriched yeast is high, but those in Se-enriched radish sprouts and in processed skipjack meats are low.

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Selenium (Se) is an essential trace element and component of glutathione peroxidase known to be involved in the reduction of free radicals. Reduction of body Se is easily induced by the external Se-deficient environment, but the symptoms of Se deficiency such as cardiomyopathy, weakness of muscle strength, muscle pain, anemia, and white nail are rarely seen in human. In this review paper, we describe that the appearance of functional disorders following Se deficiency in rats is not easily appeared, and that Se deficiency in rats reduces toxic threshold of anticancer drug “adriamycin”. And also, we consider the significance of prevention of Se deficiency based on the results of these animal studies.

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Selenium, an essential trace element for humans, presents as a selenocysteine residue in selenoproteins, such as glutathione peroxidase, thioredoxin reductase, and selenoprotein P. Selenocysteine is co-translationally incorporated into selenoproteins at an in-frame UGA codon, which usually serves as a stop codon, within the coding region of the mRNA and therefore is designated as the 21st amino acid in the genetic code. The translation of selenocysteine codon in mRNA during selenoprotein biosynthesis requires selenocysteyl (Sec)-tRNA^Sec. In general, aminoacyl-tRNA is synthesized from an amino acid and the corresponding tRNA isoacceptor in an ATP-dependent reaction catalyzed by an aminoacyl-tRNA synthetase. However, Sec-tRNA^Sec, unlike cognate aminoacyl-tRNA, is synthesized by an indirect tRNA-dependent amino acid formation mechanism. In this article, functions of several selenoproteins and enzymes involved in the biosynthetic pathway of selenoproteins are reviewed. In addition, the reaction mechanism of a selenium-specific enzyme, selenocysteine lyase, is discussed.

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Reactive chemical species involved in the single strand breaks of plasmid DNA, which was induced by sodium selenite and excess amount of reduced glutathione (GSH), were investigated. DNA damages were analyzed by agarose gel electrophoresis after DNA was incubated with selenite and glutathione in the presence or absence of several reagents to modify the level of reactive oxygen species which may be produced during the incubation in Tris-borate-EDTA (TBE) buffer (pH8.2). The addition of neither superoxide dismutase nor catalase affected the DNA damages, and the treatment of DNA with superoxide anion produced by hypoxanthine-xanthine oxidase system or exogenous hydrogen peroxide did not reproduce DNA damages induced by selenite and GSH. The results suggested that superoxide anion and hydrogen peroxide may not be the species responsible for DNA damages. Both mannitol and deferoxamine, which are expected to scavenge hydroxyl radical or inhibit hydroxyl radical production, lowered the electrophoretic band strength corresponding to open circular form, indicating that they protected the DNA from single strand breaks. DNA damages were induced by hydroxyl radical generating system of hydrogen peroxide and iron(II) ion. It was suggested that hydroxyl radical may be a species which causes DNA damages induced by selenite and GSH. In the study with isolated selenodiglutathione (GSSeSG), which is the intermediate formed by the reaction of selenite and GSH, single strand break of DNA was observed when DNA was incubated with GSSeSG and excess amount of GSH though it was not when DNA was incubated with GSSeSG alone. These results indicated that GSSeSG itself is not a species responsible for DNA damages induced by selenite and excess amount of GSH and that hydroxyl radical produced in the processes of GSSeSG decomposition with excess GSH may be a major species causing single strand breaks of DNA.

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Enteral formulas fortified with trace elements, i.e., Mn, Cr, I and Mo besides 4 trace elements, i.e., Fe, Cu, Zn and Se are now commercially available in Japan. We investigated the effects of feeding an enteral formula fortified with 8 trace elements on the blood and tissue concentrations of essential trace element in rats. Five-week-old male rats were divided into 2 groups and fed either a lyophilized commercial enteral formula fortified with 4 trace elements, i.e., Fe, Cu, Zn and Se (MEIBALANCE^®-Zcs, 4TE) or the one fortified with Mn, Cr, I, and Mo additionally to 4TE (MEIBALANCE^®, 8TE) for 4 weeks. 4TE and 8TE were equivalent in nutritional composition except for the amount of Cu, Mn, Cr, I and Mo. At the end of the experimental period, we measured 8 trace element concentrations of serum, whole blood and liver with ICP-MS. Iron, Cu, Zn and Se concentrations of serum, whole blood and liver in 8TE group were similar or higher, compared with those in 4TE group. Manganese concentrations of serum and liver were higher in 8TE group than in 4TE group. Iodine concentrations of whole blood and liver were higher in 8TE group than in 4TE group. Molybdenum and Cr concentrations of serum, whole blood and liver in 8TE group were similar to those in 4TE group. 1000 kcal of 8TE contains I, Cr and Mo at the level of Recommended Dietary Allowance and Mn at a half level of Adequate Intake of Dietary Reference Intakes for Japanese, 2005. These observations suggested that while the fortification with Mn and I resulted in increases in body content of Mn and I, the above quantities of Mn, Cr, I and Mo did not deteriorate the availability of the other 4 trace elements.

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It has been reported that human mineral and trace element intake is related to various lifestyle diseases. In order to understand the true intake of various minerals and trace elements, we surveyed the change in the level of each mineral or trace element in foodstuffs after cooking and compared the measured value with the mineral or trace element intake as estimated using a food composition table (FCT). In addition, we conducted a dietary survey and a survey on knowledge of and attitudes to mineral and trace element intake. A change in the level of most minerals and trace elements was observed after cooking. The measured levels of most minerals and trace elements were lower than the FCT-based estimates. The results of our diet survey suggested a deficiency of calcium, magnesium, and iron. The decrease after cooking was especially large for magnesium, for which the level of knowledge was also lower than for other elements. Our findings suggest the need for a more active approach to nutrition education to improve magnesium intake.

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Although the increasing industrial sources of lanthanum (La) pose potential environmental problems in recent years, the effects of La on humans and animals remain to be elucidated. This histochemical study was undertaken to elucidate whether La in drinking water is absorbed via the intestine in the rat. The experimental animals were treated with oral administrations of lanthanum chloride in drinking water (5 mg LaCl₃/ml) for 1-28 weeks. Histological paraffin sections of the intestine were stained by the alizarin complexone (ALC) method for La. Macrophages showing an ALC-positive reaction were distributed in the lamina propria of the mucous membrane of the small intestine. Electron opaque deposits were observed at an electron microscopic level in the lysosomes of the macrophages in the lamina propria of the intestinal mucous membrane. L lines of La were detected from the electron opaque deposits in the lysosomes by an electron microprobe X-ray analyzer. Thus, localization of La in the ALC-positive macrophages was confirmed by an analytical electron microscope. The ALC-positive macrophages distributed similarly in the duodenum, jejunum and ileum, but not in the large intestine. The ALC-positive macrophages were found in the small intestine even after one week of oral administration of La in drinking water. Thus, La in a drinking water is easily absorbed via the small intestine. Environmental pollution of La may be placed under close surveillance.

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