Interactive effects of selenium and chromium on mammary tumor development and growth in MMTV-infected female mice and their relevance to human cancer

Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C₃H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.     

Selenium/cadmium ratios in human prostates

Selenium (Se) in a large-scale human supplementation trial has been shown to significantly reduce the incidence of prostate cancer in elderly men. Because Se is known to interact with cadmium (Cd), it has been suggested that its cancer protective action could be attributable in part to its interaction with Cd, a toxic and suspected carcinogenic element, which is found in many foods, in drinking water, and in the environment. Cadmium is considered a significant prostate cancer risk factor as it stimulates the growth of prostate epithelial cells and promotes their malignant transformation. Accordingly, prostate cancer risk is determined not only by Se status, but also the degree of Cd exposure. Determinations of Se and Cd in 129 prostates of deceased men aged 15–99 yr revealed Cd to accumulate in the prostate. Whereas the atomic Se/Cd ratios of the prostates of young men were invariably >1, indicating a stoichiometric excess of Se over Cd, they were found to decline with age, approaching the 1∶1 ratio in elderly nonsmokers, a fact suggestive of the formation of a 1∶1 Cd−Se complex. The associated physiological inactivation of Se could account for the increase of the prostate cancer risk with advancing age. The Se/Cd ratios dropped more steeply and consistently with age in smokers than in nonsmokers. In the prostates of some smokers, Se/Cd ratios even reached values <1, indicating a stoichiometric excess of Cd over Se. The excessive accumulation of Cd in the prostates of smokers along with sub-optimal Se intakes could explain why smokers develop more aggressive and lethal forms of prostate cancer than nonsmokers.     

Chromium,selenium, and other trace element intakes of a selected sample of Canadian premenopausal women

Daily Cr, Se, Ag, Cs, Rb, Sb, and Sc intakes of 84 Canadian women aged 30.3±6.1 yr (mean±SD) living in a University community and consuming self-selected diets were determined by analyses of 1-d food composites collected by the subjects. Aliquots of the homogenized food composites were freeze-dried and then analyzed by instrumental neutron activation procedures following irradiation for 72h. In all cases, trace element concentrations in the food composites were non-Gaussian. Median daily intakes were: Cr, 47 μg; Se, 74 μg; Ag, 7.1 μg; Cs, 4.4 μg; Rb, 1.5 mg; Sb 2.0 μg; and Sc, 0.38 μg. Sixty percent and 24% of the subjects received daily Cr and Se intakes, respectively, below the US Food and Nutrition Board safe and adequate range. High Cr density diets were associated with a significantly higher consumption of cheese and dry legumes and nuts (p<0.05). In the high Se density diets, intakes of grain products and breakfast cereals were significantly higher (p<0.05), and intakes of potatoes, table fats, total fat, saturated fat, and oleic acid were significantly lower (p<0.05) compared to the low Se density diets. The low daily Cr intakes evident in this study may be cause for concern in view of the increasing evidence that women may be at greater risk for deficiency of Cr than men because of Cr depletion during pregnancy.     

Considerations on the assessment of selenium status

There is increasing interest in the techniques available for assessing Se status because of the accumulating evidence from laboratory animal experiments and human epidemiological studies that suggests a link between Se and the incidence of certain types of human cancer. In this paper, different methods of Se assessment are described, including analytical approaches (dietary intakes, tissue contents, and excreta levels), functional biochemical measurements (glutathione peroxidase activity), and functional physiological tests. The importance of considering interacting nutrients and other interacting substances is pointed out. Typical values of some Se status indicators reported in normal, deficient, and selenotic states are given.     

Selenium and selenium-antagonistic elements in nutritional cancer prevention

Selenium is an essential trace element with antioxidative, antimutagenic, antiviral and anticarcinogenic properties. There is increasing evidence that the dietary selenium intakes are sub-optimal in the populations of many countries and that human cancer mortalities would significantly decline if additional selenium was made available either through supplementation or the fortification of certain foods. An important property of selenium is its interaction with other elements that may be present in foods, the water, the workplace and the environment, e.g. As, Cu, Ni, Co, Cr, Mn, Zn, Cd, Sn, Pb, Hg, Bi, Mo, Ag, Au, etc. The sequestration of elements by selenium represents an efficient natural detoxification mechanism for some of these elements but also results in the physiological inactivation of selenium. Animal experiments confirm that the chronic exposure to low levels of these elements abolishes the cancer-protective effect of selenium. Human cancer is likewise significantly determined by the interactions of selenium with other elements, as evidenced by epidemiological, ecological and case-control studies. Cadmium, for example, is a key risk-increasing element for prostate cancer; for breast cancer, Cd, Cr, Zn are mainly contributing; for bronchial cancer (in smelter workers), Cd, As, Cr, Sb, Co, La, all these elements are in a reciprocal relationship with Se. While selenium remains the key cancer-protective trace element, the interpretation of its mode of action necessitates consideration of the effects of selenium antagonistic elements.     

Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells

Selenium (Se) is a potential anticarcinogenic nutrient, and the essential role of Se in cell growth is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se-deficiency. To understand the molecular basis of Se-anticancer effects at nutritional doses (nmol/L) for cultured cells, we generated Se-deficient colon Caco-2 cells by gradually reducing serum in media because serum contains a trace amount of Se. The glutathione peroxidase (GPx) activity of Se-deficient Caco-2 cells was 10.8 mU/mg protein compared to 133.6 approximately 146.3 mU/mg protein in Caco-2 cells supplemented with 500 nmol/L selenite, SeMSC or SeMet (three tested Se-chemical forms) after 7-d culture in serum free media. Interestingly, there were no detectable differences in cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se. To examine differential cancer signaling-gene expression between Se-deficient and Se-supplemented cells, we employed a cancer signal pathway-specific array assay coupled with the real time PCR analysis. Our data demonstrate that although Caco-2 cells are resistant to Se deprivation, Se may exert its anticancer property through increasing the expression of humoral defense gene (A2M) and tumor suppressor-related genes (IGFBP3, HHIP) while decreasing pro-inflammatory gene (CXC L9, HSPB2) expression.     

The Role of Microorganisms in Transformation of Selenium in Marine Waters

The activity of microorganisms is a decisive factor in the transformation of the essential and, at the same time, toxic selenium (Se) in marine waters. This review provides an analysis of the literature data on the microbiological regulation of the state of Se in marine waters: the role of microorganisms in eliminating toxic Se from marine waters through precipitation of reduced Se forms and in the reverse process, transformation of Se into a form available to be taken up by organisms and involvement of this element in the biogeochemical cycle. The processes of transformation of the oxidized and reduced Se forms with the participation of microorganisms in marine waters are considered. It has been shown that in anaerobic conditions bacteria use the oxidized Se forms as electron acceptors (reduction). Bioavailable selenite and selenate ions are formed in the case of aerobic oxidation. Biotransformation of dissolved Se is a key mechanism for the formation of methylated gaseous Se forms in marine waters as one of the ways to remove this element from the aquatic environment.     

植物硒生理及与重金属交互的研究进展

硒是一种重要的微量元素,在低浓度时对生物有益,但高浓度时呈现与重金属类似的毒性。植物作为人体硒摄入的主要来源,其硒代谢对于植物硒积累乃至人体硒营养水平十分重要。研究植物硒吸收、代谢和积累机理能指导富硒粮食的生产,是解决人体硒摄入不足/超量问题的有效途径。本文在阐述土壤硒含量、形态、生物有效性及分布的基础上,综述了植物对硒的吸收、代谢机理的研究进展,并讨论了农业生物强化以及遗传育种生物强化等两种硒生物强化的实践方法,以及利用硒生物强化缓解重金属毒性减少积累;最后,提出了植物硒代谢及硒生物强化研究的前沿问题,以期为改善人体硒营养水平提高人体健康状况提供理论和实践依据。     

Chemoprevention of cancer: selenium

1. Selenium intake (in the form of selenite, selenate, selenomethionine, etc.) protects the organism against the action of some kinds of carcinogens. 2. People and animals having less Se in their blood are at a higher risk of acquiring cancer than those whose blood contains more of this element. 3. This chemopreventive action is probably due to antioxidant properties of Se, its involvements in the enzyme glutathione peroxidase as well as in the inhibition of enzymes converting carcinogens to their ultimate forms in the cell. 4. An intake of 150-300 micrograms of Se daily is considered to be adequate to protect the human organism without exhibiting the toxic properties of this element.     

Effect of supplementation with selenium on whole blood glutathione peroxidase activities and on plasma and tissue selenium concentrations in lambs

In recent years the selenium (Se) intake of the human population of the UK has shown a marked decline from 60 μg/d in 1978 to around 30 μg/d in 1990 owing largely to a significant reduction in the importation of North American wheat for bread-making fluor. Other countries (Finland, for example) in similar situations have instituted fertilization programs in order to raise cereal Se concentrations and thus boost dietary intakes. An alternative approach would be to increase the Se concentration of carcass meat by supplementation of meat animals for a limited period prior to slaughter. A trial was set up with store lambs to evaluate this approach. Sixteen Scottish Blackface lambs were stratified according to live weight and then randomly allocated to one of four treatments: unsupplemented, or 3.5, 7, or 10.5 mg. Se/head/wk. After 14 wk, the lambs were sacrificed and samples of shoulder and thigh muscle, liver, and kidney were obtained for analysis. All three treatments effected an increase in whole blood glutathione peroxidase (GSH-Px) and plasma Se concentrations over controls. Shoulder, thigh, and liver Se exhibited a dose-response relationship to treatment, but kidney Se concentrations were unaffected by treatment. Muscle and some organ meat Se concentrations can therefore be increased by supplementation and could contribute to increased human dietary intakes of the element.     

Microbial Transformations of Selenium and the Bioremediation of Seleniferous Environments

Selenium (Se) exists in many natural soil and water environments around the world, but anthropological activities such as irrigated agriculture on Se-laden soils has created many ecological problems with respect to this element. Seleniferous agricultural drainage water in California's San Joaquin Valley has been linked to the death and deformity of waterfowl. In the environment, microbial reduction, oxidation, methylation, and demethylation reactions predominantly control the oxidation state of Se and its subsequent behavior. In an effort to remediate these Se-contaminated environments a number of biological technologies have been investigated. Biological transformations of toxic Se oxyanions into less toxic or biologically unavailable forms, such as elemental Se or volatile Se compounds, has received much attention over the last decade. In this literature review, a major emphasis is placed on Se reduction and methylation/volatilization reactions because these processes are currently the most promising techniques being investigated for the bioremediation of seleniferous soil and water.     

The interplay between sulphur and selenium metabolism influences the intracellular redox balance in Saccharomyces cerevisiae

Selenium (Se) is an essential element for most eukaryotic organisms, including humans. The balance between Se toxicity and its beneficial effects is very delicate. It has been demonstrated that a diet enriched with Se has cancer prevention potential in humans. The most popular commercial Se supplementation is selenized yeast, which is produced in a fermentation process using an inorganic source of Se. Here, we show that the uptake of Se, Se toxic effects and intracellular Se-metabolite profile are largely influenced by the level of sulphur source supplied during the fermentation. A Yap1-dependent oxidative stress response is active when yeast actively metabolizes Se, and this response is linked to the generation of intracellular redox imbalance. The redox imbalance derives from a disproportionate ratio between the reduced and oxidized forms of glutathione and also from the influence of Se metabolism on the central carbon metabolism. The observed increase in glycerol production rate, concomitant with the inhibition of ethanol formation in the presence of Se, can be ascribed to the occurrence of redox imbalance that triggers glycerol biosynthesis to replenish the pool of NAD(+) .     

An analysis of cancer prevention by selenium

The nutritional functions of selenium (Se) are recognized as being due to a number of Se-containing proteins. It is not clear, however, whether any of these function in the anti-tumorigenic effects of Se most of which have been demonstrated for Se exposures greater than those required for selenoprotein expression. Indeed, other anti-tumorigenic mechanisms have been demonstrated for certain Se-metabolites. The Nutritional Prevention of Cancer Trial found supplemental Se (200 microg/day, as Se-enriched yeast) to be associated with significant reductions in cancer risks in subjects with pre-treatment plasma Se concentrations below ca. 120 ng/ml (1.5 nmoles/ml), which level would appear to require food-Se intakes of ca. 1.5 microg/kg body weight/day. However, the putative anti-carcinogenic Se-metabolite(s) should be more relevant than total plasma Se as a supplementation target for cancer prevention. These may be components of the non-protein-bound fraction of Se in plasma, which constitutes 2-4% of total plasma Se.     

A study of inter- and intrasubject variability in seven-day weighed dietary intakes with particular emphasis on trace elements

In this study of inter- and intrasubject variance of trace element (TE) dietary intake data, 14 female university students recorded weighed, self-selected food intakes for seven consecutive days, starting on a randomly selected day of the week. Daily intakes of energy, dietary fiber, macronutrients, 7 vitamins, and Fe, Zn, Cu, Mn, and Se were calculated using food composition tables and literature values. Analysis of variance showed a significant weekend effect for energy and TE intakes that was reduced when data were expressed on the basis of nutrient densities. No day of the working week or training effect was noted for energy or any nutrient. The ratios of the inter- to intrasubject coefficient of variation for all the nutrients were surprisingly constant. However, the overall coefficients of variation—Fe, 36.5%; Zn, 45.7%; Cu, 43.7%; Mn, 58.2%, and Se, 52.7%—were markedly lower than for vitamin A (109.0%), Vitamin D (117.1%), and linoleic acid (82.2%), but slightly higher than those for energy (27.2%) and carbohydrate (30.1%). The widespread distribution of TE in the diets results in comparable reliability for dietary studies of TE and macronutrients. The 95% confidence intervals for mean individual TE intakes ranged from 25% (Zn) to 40% (Se). These relatively large uncertainties make it essential that any assessment of the significance of correlations between dietary TE intakes and biochemical indices takes into account the intra-individual variation associated with both variables.     

Selenium (Se) from high-selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis

The reduction in incidence of chemically-induced colon cancer by foods high in selenium (Se) was investigated in Fisher-344 rats. The foods used were high-Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high-Se wheat product (made by milling high-Se wheat purchased from a seleniferous area). Weanling rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the experiment the animals were injected with a chemical carcinogen. After 11 weeks on diets animals were killed and the colons examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were significantly reduced in animals fed supra-nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra-nutritional amounts of Se from high-Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine, (the predominant chemical form of Se in wheat), did not significantly reduce AC. These results emphasize the need to study Se in food forms, and not extrapolate from previous studies using pure chemical forms in cancer inhibition studies. They also demonstrate that foods with high Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.     

Current knowledge on potential health benefits of Spirulina

Spirulina is a microscopic filamentous alga that is rich in proteins, vitamins, essential amino acids, minerals and essential fatty acids like γ-linolenic acid (GLA). It is produced commercially and sold as a food supplement in health food stores around the world. Up to very recently, the interest in Spirulina was mainly in its nutritive value. Currently, however, numerous people are looking into the possible therapeutic effects of Spirulina. Many pre-clinical studies and a few clinical studies suggest several therapeutic effects ranging from reduction of cholesterol and cancer to enhancing the immune system, increasing intestinal lactobacilli, reducing nephrotoxicity by heavy metals and drugs and radiation protection. This paper presents a critical review of some published and unpublished data on therapeutic effects of Spirulina.     

Tracking Se Assimilation and Speciation through the Rice Plant – Nutrient Competition,Toxicity and Distribution

Up to 1 billion people are affected by low intakes of the essential nutrient selenium (Se) due to low concentrations in crops. Biofortification of this micronutrient in plants is an attractive way of increasing dietary Se levels. We investigated a promising method of Se biofortification of rice seedlings, as rice is the primary staple for 3 billion people, but naturally contains low Se concentrations. We studied hydroponic Se uptake for 0–2500 ppb Se, potential phyto-toxicological effects of Se and the speciation of Se along the shoots and roots as a function of added Se species, concentrations and other nutrients supplied. We found that rice germinating directly in a Se environment increased plant-Se by factor 2–16, but that nutrient supplementation is required to prevent phyto-toxicity. XANES data showed that selenite uptake mainly resulted in the accumulation of organic Se in roots, but that selenate uptake resulted in accumulation of selenate in the higher part of the shoot, which is an essential requirement for Se to be transported to the grain. The amount of organic Se in the plant was positively correlated with applied Se concentration. Our results indicate that biofortification of seedlings with selenate is a successful method to increase Se levels in rice.