Effect of selenium on virally induced and transplantable tumor models

Se is effective in inhibiting both virally induced and transplantable tumors. Continued intake of Se at quantities greater than those required to optimize growth and glutathione peroxidase (EC 1.11.1.9) activities appear to be needed to achieve maximal tumor inhibition. Differences in the sensitivity to Se of various tumor cell lines are evident. The efficacy of Se depends on the form and mode of administration of this trace element. Total tumor mass also appears to affect the efficacy of Se. Evidence now suggests that selenodiglutathione or some other intermediate in Se metabolism is responsible for the antitumorigenic properties of this trace element.     

Bioavailability and possible benefits of wheat intake naturally enriched with selenium and its products

Bioavailability and possible benefits of wheat intake naturally enriched with selenium and its products was tested. Wheat obtained by application of an original combination and procedure for foliar supplementation of plants with Se was characterized on the average by five times higher content of Se, the main form being l-(+)-selenomethionine (SeMet). Substitution of Se-deficient wheat by wheat naturally enriched with Se and its products contributed to the increase of daily intake on the average by 18 μg (12–35 μg) in volunteers, which is more than 50% of the average daily intake. Six weeks after the beginning of its application, increased daily intake of Se brought about the increase of its concentration in the plasma of the examined persons by 53%, in their erythrocytes by 37%, in their hair by 44%, and in their urine by 54%. This result was comparable to the effect obtained in the course of an 8-wk daily intake of supplements with 100 μg Se in the form of enriched bakery yeast. Analysis of glutathione peroxidase (GSH-Px) activity in blood, thiobarbituric acid reactive substances (TBARS) in plasma, lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), and glucose in serum of volunteers showed that the increased Se intake induced increased GSH-Px activity in blood and decreased concentrations of TBARS, lipid parameters, and glucose in blood. Using only one crop (wheat enriched with Se), the existing deficiency of Se in our population can be alleviated. In this way, one-fourth of our population with lower Se intake than 21 μg/d will satisfy basal requirements, whereas one-half will become moderately deficient in Se instead of distinctly deficient in Se.     

Chemoprevention of cancer: phenolic antioxidants (BHT, BHA)

1. The synthetic phenolic antioxidants (e.g. BHT, BHA) added to human and animal food are able to lengthen the life of organisms and lower the incidence of cancer caused by chemical compounds. 2. On the other hand they may not be rendered completely harmless since they can cause lung damage (BHT) or promote the action of some carcinogens (BHA). 3. They could act as compounds preventing cancer either via interception of harmful free radicals, activating the detoxifying enzymes of the body, inhibiting the formation of ultimately carcinogenic metabolites and their binding to DNA, and modifying the immune response of the organism. 4. Their action is influenced by their own chemical structure, the composition of carcinogen, the strain, sex and age of experimental animals, the tissue upon which they are supposed to act and the time of their administration in relation to the time of the carcinogen insult. 5. These compounds are concentrated in adipose tissue, liver and kidney. They are excreted within tens of hours mainly in urine. 6. The acceptable daily intake of BHA is at present considered to be 0.6 mg kg-1 body wt day-1. In spite of their possible tumor-promoting properties they could not be considered overtly toxic. Their pronounced chemoprotective role against some forms of chemical carcinogenesis deserves considerable attention.     

Evaluation of a DNA polymerase-deficient mutant of E. coli for the rapid detection of carcinogens

Differential growth inhibition of two E. coli cultures was evaluated as a rapid screening technique for chemical carcinogens. Of the carcinogens tested, only “direct acting” carcinogens produced positive results. Furthermore, this test is not a quantitative assay in that neither was a dose—response relationship seen nor did potent carcinogens necessarily show a greater response than weaker carcinogens.Most of the carcinogens tested are considered to require metabolic activation in order to exert their carcinogenic action. Despite many attempts, including several variations of reaction conditions, metabolic activation by rat liver fractions was not apparent. Many of these carcinogens are insoluble in water and may not diffuse through the agar and therefore not reach the indicator organism.A number of chemicals that are not carcinogenic produced positive results with this assay. Many of these substances are oxidants or oxidation products which are highly reactive with DNA as well as with other cellular constituents. Therefore, it is possible that the toxicity exhibited by these chemicals was caused by a reaction with some essential cellular constituent other than DNA and such damage would not be repairable by DNA polymerase. These observations limit the usefulness of the P3478 E. coli technique in its present form as a prescreen for chemical carcinogens.     

Selenium inhibition of chemical carcinogenesis

In this article I review the work of our laboratory concerning the relationship between dietary Se intake and susceptibility to mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in female rats. The effect of graded levels of Se in the diet was investigated, ranging from deficiency to excessive supplementation that produced marginal toxicity in the animals. In addition, the interdependence between Se status and fat intake was also explored. Further experiments were aimed at defining the role of Se in the initiation and promotion phases of chemical carcinogenesis. In view of the biochemical function of Se as an antioxidant, the chemopreventive efficacy of Se was compared to that of vitamin E in conjunction with their ability to inhibit lipid peroxidation. Results of this study indicated that the antitumorigenic activity of Se could not be accounted for by suppression of tissue peroxidation, although an environment with a lower oxidant stress might enhance the potency of Se in protecting against cancer. The possible mechanisms of action of Se based on the observations and characteristics of several tumor models are briefly discussed.     

Gestational changes in concentrations of selenium and zinc in the porcine fetus and the effects of maternal intake of selenium

The effect of maternal dietary selenium (Se) and gestation on the concentrations of Se and zinc (Zn) in the porcine fetus were determined. Mature gilts were randomly assigned to treatments of either adequate (0.39 ppm Se) or low (0.05 ppm Se) dietary Se. Gilts were bred and fetuses were collected throughout gestation. Concentrations of Se in maternal whole blood and liver decreased during gestation in sows fed the low-Se diet compared to sows fed the Se-supplemented diet. Maternal intake of Se did not affect the concentration of Se in the whole fetus; however, the concentration of Se in fetal liver was decreased in fetuses of sows fed the low-Se diet. Although fetal liver Se decreased in both treatments as gestation progressed, the decrease was greater in liver of fetuses from sows fed the low-Se diet. Dietary Se did not affect concentrations of Zn in maternal whole blood or liver or in the whole fetus and fetal liver. The concentration of Se in fetal liver was lower but the concentration of Zn was greater than in maternal liver when sows were fed the adequate Se diet. These results indicate that maternal intake of Se affects fetal liver Se and newborn piglets have lower liver Se concentrations compared to their dams, regardless of the Se intake of sows during gestation. Thus, the piglet is more susceptible Se deficiency than the sow.     

Blood Selenium in Naturally Fed Horses and the Effect of Selenium Administration

Blood Se of adult horses was 26.1, 25.8, and 27.0 ng/ml (mean values at 3 farms), where the Se of food was about 20 ng/g dry substance. Experimental adult horses which received about 41 ng Se/g food showed 45.3 ng/ml blood. At low Se intake suckling foals show higher blood Se than mares, but with high Se intake, the opposite will occur. This is reflected in milk Se, which raises but slowly with rise of mare’s blood Se. Se in blood plasma and in blood corpuscles is on the same level. The effect of various dose levels of Se on blood Se was studied: From 1.5 to 6 mg Se/week, blood Se rose rather linearity; 18 and 30 rag Se/week gave but slightly more effect than 6 mg.     

人体硒代谢与硒营养研究进展

硒是人体所必需的重要微量营养元素,综述了当前国内外人体硒代谢与硒营养的研究进展,包括硒源形式与吸收、人体的硒含量与分布、硒的代谢途径、硒的生物活化形式、硒与疾病、硒中毒和硒的安全摄入量。在此基础上,提出了针对我国硒资源分布、硒反应症分布和居民膳食结构硒摄入量的研究建议,为满足居民通过膳食和补充剂补硒预防和治疗疾病提供理论和实践指导。     

Effect of dietary selenium and tumor status on the retention of75Se by tissues and mammary tumors of DMBA-treated rats

The effects of the presence of mammary tumors on 75Se retention was examined in DMBA-treated rats. Tumor bearing rats fed varying amounts of Se exhibited an inverse linear dose response between dietary Se intake and tissue retention of 75Se in whole body, heart, lungs, ovaries, adrenals, spleen, and muscle. Tumor 75Se retention, however, was independent of the dietary intake of Se. Tumor bearing rats excreted more 75 Se label in the urine compared to both control rats fed the same amount of Se and DMBA-treated animals that remained tumor free. In the short term, no significant differences were seen in tissue retention of 75Se. By 7 d, the increased urinary excretion of the label resulted in significantly decreased retention of 75Se in blood, spleen, liver, lungs, and kidneys of tumor-bearing rats compared to tumor-free animals. The presence of tumors, however, did not affect the liver distribution of the label among cytosolic proteins. These results suggest that tumor bearing animals have an accelerated urinary excretion of Se compared to animals without tumors and that tumors either have a very slow turnover of Se or a low priority for the element.     

Correlations of Trace Element Levels in the Diet,Blood, Urine,and Feces in the Chinese Male

In order to explore the associations between trace elements in dietary intake and the other three biological media (blood, urine, or feces) and inter-element interactions among the latter, we simultaneously collected 72-h diet duplicates, whole blood, and 72-h urine and feces from 120 free-living healthy males in China. Correlations among the toxic (cadmium [Cd], lead [Pb]), and nutritionally essential (zinc [Zn], copper [Cu], iron [Fe], manganese [Mn], selenium [Se], iodine [I]) elements were evaluated using Spearman rank correlation analysis based on analytical data determined by inductively coupled plasma-mass spectrometry. Dietary Cd intakes were highly correlated with the fecal Cd and blood Cd levels. Inverse correlations were found for Fe–Cd and Fe–Pb in both diet versus blood and diet versus feces. Cd–Zn and Cd–Se were significantly directly correlated in the urine and feces. Cd–Se and Pb–Se were negatively correlated in blood. In addition, there existed an extremely significant association between urinary Se and urinary I. Moreover, the other two highly direct correlations were found for Se–Fe and for I–Fe in urine. Improved knowledge regarding their mutual associations is considered to be of fundamental importance to understand more the complex interrelationships in trace element metabolism.     

Selenium, oxidative stress, and health aspects

Metabolic processes which generate oxidants and antioxidants are governed by genetic disposition as well as environmental factors. Changes in lifestyle, including increased environmental pollution, sun exposure, and dietary habits modify the challenge of the organism by reactive oxygen species. Defense mechanisms are reinforced by increasing dietary intake of antioxidants and micronutrients such as vitamins and selenium (Se). Se deficiency has been recognized to promote some disease states. Epidemiological findings link a lowered Se status to neurodegenerative and cardiovascular diseases as well as to increased cancer risk. While evidence exists to suggest that additional selenocompounds would be beneficial in some health conditions, results from future intervention trials are needed to substantiate the argument for increasing Se intake. Several pieces of the puzzle concerning the molecular mechanisms underlying the reactive oxygen species-triggered disease state and intervention by enzymatic antioxidants have been elucidated. A novel concept of protection of stromal cells against the dominating influence of tumor cells in tumor-stroma interaction by selenocompounds and other antioxidants is presented herein, which may translate into therapeutic strategies in chemoprevention of tumor invasion.     

Biogeochemistry of selenium and its impact on food chain quality and human health

In areas where soils are low in bioavailable selenium (Se), potential Se deficiencies cause health risks for humans. Though higher plants have been considered not to require this element, the experience with low-Se soils in Finland has provided evidence that the supplementation of commercial fertilizers with sodium selenate affects positively not only the nutritive value of the whole food chain from soil to plants, animals and humans but also the quantity of plant yields. The level of Se addition has been optimal, and no abnormally high concentrations in plants or in foods of animal origin have been observed. Se levels in serum and human milk indicate that the average daily intake has been within limits considered to be safe and adequate. In fact, plants act as effective buffers, because their growth is reduced at high Se levels. They also tend to synthesize volatile compounds in order to reduce excess Se. On the other hand, when added at low concentrations, Se exerts a beneficial effect on plant growth via several mechanisms. As in humans and animals, Se strengthens the capacity of plants to counteract oxidative stress caused by oxygen radicals produced by internal metabolic or external factors. At proper levels it also delays some of the effects of senescence and may improve the utilization of short-wavelength light by plants. High additions are toxic and may trigger pro-oxidative reactions. Thus, the present supplementation of fertilizers with Se can be considered a very effective and readily controlled way to increase the average daily Se intake nationwide.     

Fish arsenic may influence human blood arsenic,selenium, and T4:T3 ratio

The effects of an arsenic-rich fish diet and selenium (Se) supplementation on blood arsenic (As), Se, and thyroid hormones were studied in 32 women divided into four equal groups. Groups 1 and 4 received 400 μg Se-methionine daily, group 2 received 400 μg selenite daily, and group 3 received placebo tablets for 15 wk. In addition, groups 1–3 increased their fish intake, eating at least three fish dinners weekly. Mean blood Se concentrations (initially 1.68 ± 0.24 μmol/L) increased twofold in the Se-methionine groups (p < 0.0001) and by 32% in the selenite group (p < 0.01). Group means of blood As concentrations increased by 63% (p < 0.01), 50% (p < 0.01), 106% (p < 0.01), and 29% (p < 0.05) in the four groups, respectively. Analyzed As intake from duplicate portions of consumed fish correlated with final blood As concentrations (r=0.85, p < 0.001, n=32). In the group not receiving Se, there was a positive correlation between final blood As concentrations and plasma T4 : T3 ratio (r=0.80, p < 0.02, n=8). Initially, blood As concentrations correlated negatively with both T3 and T4 in plasma, but this correlation disappeared upon Se supplementation. The results demonstrate that increased intake of fish may influence blood As concentrations and that circulating thyroid hormones may be influenced by Se-As interactions.     

Biogeochemistry of selenium and its impact on food chain quality and human health

In areas where soils are low in bioavailable selenium (Se), potential Se deficiencies cause health risks for humans. Though higher plants have been considered not to require this element, the experience with low-Se soils in Finland has provided evidence that the supplementation of commercial fertilizers with sodium selenate affects positively not only the nutritive value of the whole food chain from soil to plants, animals and humans but also the quantity of plant yields. The level of Se addition has been optimal, and no abnormally high concentrations in plants or in foods of animal origin have been observed. Se levels in serum and human milk indicate that the average daily intake has been within limits considered to be safe and adequate. In fact, plants act as effective buffers, because their growth is reduced at high Se levels. They also tend to synthesize volatile compounds in order to reduce excess Se. On the other hand, when added at low concentrations, Se exerts a beneficial effect on plant growth via several mechanisms. As in humans and animals, Se strengthens the capacity of plants to counteract oxidative stress caused by oxygen radicals produced by internal metabolic or external factors. At proper levels it also delays some of the effects of senescence and may improve the utilization of short-wavelength light by plants. High additions are toxic and may trigger pro-oxidative reactions. Thus, the present supplementation of fertilizers with Se can be considered a very effective and readily controlled way to increase the average daily Se intake nationwide.     

Individual Intake of Free-Choice Mineral Mix by Grazing Beef Cows May Be Less Than Typical Formulation Assumptions and Form of Selenium in Mineral Mix Affects Blood Se Concentrations of Cows and Their Suckling Calves

The objectives of this study were to determine (1) the individual ad libitum intake of mineral mix by beef cows managed under a year-long, fall-calving, forage-based production regimen and (2) if Se form in the mineral mix affected the blood Se concentrations of cows and suckling calves. Twenty-four late-gestation (6 to 8 months) Angus-cross cows (2.7?±?0.8 years; body weight [BW]?=?585?±?58 kg) were blocked by BW and randomly assigned (n?=?8) to a mineral supplement treatment (TRT) containing 35 ppm Se as either inorganic (ISe; sodium selenite), organic (OSe; Sel-Plex®), or a 1:1 combination of ISe/OSe (MIX). Cows commonly grazed a 10.1-ha predominately tall fescue pasture and had individual ad libitum access to TRT using in-pasture Calan gates. Cows calved from August to November and calves had common ad libitum access to creep feed and a mineral supplement that lacked Se. Cow jugular blood was taken at 28-day intervals (13 periods) and calf blood was taken with cows from birth through weaning. Individual cow mineral mix (mean?=?54.0?±?7.0 g/day, range?=?97.3 to 27.9?±?7.4 g/day) and Se (mean?=?1.82?±?0.25 mg/day, range?=?3.31 to 0.95?±?0.25 mg/day) intakes were affected by period (P?<?0.0001), but not by cow Se TRT (P?>?0.30). Cow blood Se (0.109 to 0.229?±?0.01 μg/mL) was affected (P?<?0.002) by period, Se form, and their interaction, with ISe?< MIX for periods 8 and 11, ISe?<?OSe for all periods except period 1, and MIX?<?OSe for periods 2 to 4, 7, 8, 10, and 12. Calf blood Se (in micrograms Se per milliliter) was correlated with cow blood Se and affected (P?<?0.0001) by cow Se TRT, with ISe (0.07 to 0.11)?<?MIX (0.10 to 0.15)?=?OSe (0.16 to 0.19). These data reveal that (1) mean supplemental ad libitum cow mineral intake was 36 % less than the typical formulation intake expectations (85 g/day) and, correspondingly, mean supplemental Se intake was 33 % less than that allowed by the FDA and (2) cow Se TRT differentially affected both cow and calf blood Se concentrations, resulting in adequate concentrations for all cows but inadequate concentrations for ISe calves.     

Effects of selenium on chemical carcinogenesis

Chemical carcinogenesis can be characterized by a sequence of events leading to the development of tumors. Selenium (Se) inhibition of colon, liver, and lung carcinogens is demonstrated. Using the male Sprague Dawley rat model Se inhibited the colon tumor incidence in 1,2-dimethylhydrazine (DMH) treated rats and reduced the total number of colon tumors in methylazoxymethanol (MAM) treated rats. Selenium inhibited 2-acetylaminofluorene (AAF) and 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB) hepatocarcinogenesis. The hepatic tumor incidence induced by 3′-MeDAB was reduced by both inorganic Se (Na₂SeO₃) and by organic Se (Se-yeast) supplements. In vitro systems have been studied in an effort to decipher the inhibitory properties of Se on the multistage origin of tumors induced by chemical carcinogens. Current studies suggest that the protective effect of Se against AAF hepatocarcinogenesis may be correlated with a change in AAF metabolism. The mutagenicity of AAF and AAF metabolites inSalmonella typhimurium TA1538 is decreased by Se. Additionally, Se reduced N-t-OH−AAF induction of sister chromatid exchange (SCE) frequencies in whole blood cultures, and also reduced aryl hydrocarbon hydroxylase activity using benzo(a) pyrene as substrate. The comparative effects of antioxidants on DMH induction of colon tumors are presented in detail. Supplements of 4 ppm Se to the drinking water, 1.2% ascorbic acid (V _c ) to the diet or 0.5% butylated hydroxytoluene (BHT) to the diet of DMH-treated rats reduced the colon tumor incidence of DMH controls from 64 to 31% (Se), 38% (V _c ), and 43% (BHT). The colon tumor incidence in DMH-treated rats receiving a combination of Se+V _c increased to 83%, while the combination of Se+BHT decreased the colon tumor incidence to 55%. The growth and survival of rats provided long-term supplements of 4 ppm Se in the drinking water are compared with untreated controls.     

Selenium, a versatile trace element: current research implications

Selenium (Se), a trace element, has evolved from its toxic properties to an essential element. Se was known a potent antioxidant through glutathione peroxidase (selenium being part of this molecule). Later, many other selenium-binding proteins were discovered and their functions were tried to be known with unsuccessful results in many cases. Se is known to be involved in carcinogenesis, immune function, male reproduction, cardiovascular diseases etc. The specific mechanism of the involvement of the element is still not known. Recent research with application of modern research tools viz. bioinformatics, cDNA microarray and transgenesis have revealed the mechanism of selenium involvement in various processes. This review highlights mysterious and useful roles of selenium in biological processes.