Efficacy of dietary selenium sources on growth and carcass characteristics of growing-finishing pigs fed diets containing high endogenous selenium.

A study was conducted to determine the efficacy of organic (Se-yeast, SelenoSource AF, Diamond V Mills Inc., Cedar Rapids, IA) and inorganic sources of Se on growth performance, tissue Se accretion, and carcass characteristics of growing-finishing pigs fed diets with high endogenous Se content. A total of 180 pigs at 34.4 +/- 0.06 kg of BW were allotted to 1 of 5 dietary treatments: a negative control without added Se (NC); 3 treatment diets with 0.1, 0.2, or 0.3 mg/kg of added Se from an organic source; and a diet with 0.3 mg/kg of added Se as sodium selenite. Each treatment had 6 pens, with 6 pigs per pen-replicate. Experimental diets were changed twice at 66.1 +/- 0.5 kg and 99.0 +/- 0.9 kg of BW, and were fed until the pigs reached market weight. Growth performance was measured at the end of each phase. Upon reaching 129.9 +/- 1.4 kg of BW, the pigs were transported to a local abattoir (Seaboard Foods, Guymon, OK), where carcass, loin, and liver samples were obtained. Hair and blood samples were obtained at the beginning and end of the study for Se analysis. Growth performance did not differ (P > 0.05) among treatments. Percent drip loss of the NC pigs was greater (2.41 vs. 1.75, P = 0.011) compared with pigs supplemented with Se. Pigs fed diets with added Se had greater Se concentrations in the liver (0.397 vs. 0.323 ppm, P = 0.015), loin (0.236 vs. 0.132 ppm, P < 0.001), serum (0.087 vs. 0.062 ppm, P = 0.047), and hair (0.377 vs. 0.247 ppm, P = 0.003) compared with the NC pigs. Percentage drip loss was linearly reduced [percent drip loss = 2.305 - (2.398 x Se), r2 = 0.29, P = 0.007] as dietary organic Se concentration increased. The Se concentration (ppm) in the liver [liver Se = 0.323 + (0.291 x Se), r2 = 0.33, P = 0.003], loin [loin Se = 0.122 + (0.511 x Se), r2 = 0.57, P < 0.001], serum [serum Se = 0.060 + (0.113 x Se), r2 = 0.33, P = 0.004] and hair [hair Se = 0.237 + (0.638 x Se), r2 = 0.56, P < 0.001] increased linearly as dietary organic Se concentration increased. Slope ratio analysis indicated that the relative bioavailability of organic Se for percent drip loss and loin and hair Se response was 306, 192, and 197% of that for inorganic Se, respectively. The results of the study show a potential advantage of organic Se supplementation in reducing drip loss even when the basal diet contains an endogenously high Se concentration of 0.181 ppm.

Dimethyldiselenide and methylseleninic acid generate superoxide in an in vitro chemiluminescence assay in the presence of glutathione: implications for the anticarcinogenic activity of L-selenomethionine and L-Se-methylselenocysteine.

The reduction of cancer incidence by dietary supplementation with L-selenomethionine, L-Se-methylselenocysteine, and other methylated selenium compounds and metabolites is believed to be due to the metabolic generation of the monomethylated selenium species methylselenol. Dimethyldiselenide and methylseleninic acid were reduced by glutathione in an in vitro chemiluminescent assay in the presence of lucigenin for the detection of superoxide (O2-.). The methylselenol produced on reduction of dimethyldiselenide and methylseleninic acid was found to be highly catalytic, continuously generating a steady state of O2-. The O2-. detected by the chemiluminescence generated by methylselenol was fully quenched by superoxide dismutase, causing a complete cessation of chemiluminescence. In contrast, dimethyldisulfide in the presence of glutathione was not catalytic to any measurable extent and did not generate any superoxide. These in vitro results suggest that methylselenol catalysis is possible in vivo, and if metabolism generates sufficient concentrations of methlylselenol from L-selenomethionine or L-Se-methylselenocysteine in vivo, it could change the redox status of cells and oxidatively induce cellular apoptosis.

Effect of dietary copper on selenium toxicity in Fischer 344 rats.

The purpose of this study was to investigate the ameliorating effects of dietary copper supplementation on selenium toxicity. Nine groups (n = 6) of weanling Fischer 344 female rats were randomly assigned to treatment groups and fed diets containing nontoxic levels of copper as CuCl2 and/or selenium as selenite or selenocystamine. Weight gain, liver and spleen weights, plasma lipid peroxidation, and liver selenium and copper content were analyzed after the 6-wk treatment period. Concentrations of up to 10 times the daily lethal dose of dietary selenium were well tolerated in rats supplemented with dietary copper. As the dietary level of selenium was increased, the ratio of selenium to copper measured in the liver decreased. In the groups of rats in which dietary copper supplementation was absent and dietary selenium was supplemented, copper stores in the liver remained unchanged from control values. Copper's protective effects from dietary selenium toxicity may come from the formation of a copper-selenide complex that renders both selenium and copper metabolically unavailable and nontoxic.

Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis.

The cancer chemopreventive effect of selenium cannot be fully accounted for by the role of selenium as a component of the antioxidant enzyme glutathione peroxidase, which suggests that chemoprevention occurs by another mechanism. Several studies have shown that thiol oxidation and free radical generation occur as a consequence of selenium catalysis and toxicity. In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis. The experimental results suggest that, in addition to supporting an increased activity of glutathione peroxidase, an antioxidant function that the three selenium compounds did with equal efficacy, catalytic selenite, and selenocystamine generated 8-hydroxydeoxyguanosine DNA adducts, induced apoptosis and were found to be cytotoxic in mouse keratinocytes. The noncatalytic selenomethionine was not cytotoxic, did not generate 8-hydroxydeoxyguanosine adducts and did not induce cellular apoptosis at any of the selenium concentrations studied. In keratinocytes, apoptosis may be initiated by superoxide (O2*-) and oxidative free radicals that are generated by selenite and selenocystamine, but not by selenomethionine.

Inhibition of selenite-induced cytotoxicity and apoptosis in human colonic carcinoma (HT-29) cells by copper.

Selenite catalytically oxidizes reduced glutathione (GSH) with subsequent generation of superoxide. Our laboratory has previously shown that this selenite-catalyzed generation of superoxide is strongly inhibited by copper [as copper(II) sulfate]. In the present study we have demonstrated that exposure of human colonic carcinoma cells (HT-29) to selenite resulted in the induction of apoptosis, DNA fragmentation, an increase in intracellular levels of the antioxidant GSH, and cytotoxicity. Selenite-induced apoptosis, DNA fragmentation, increases in GSH levels, and cytotoxicity were inhibited by copper(II) sulfate. Copper only protected cells from selenite cytotoxicity when cells were exposed to selenite and copper simultaneously, not when cells were pretreated with copper, then washed before selenite exposure. This suggests that copper elicits its protective effect extracellularly. Previous data reported by this laboratory clearly demonstrated that copper inhibited selenite-catalyzed superoxide generation. Collectively, these data suggest that reactive oxygen species may play a role in selenite-induced cytotoxicity, apoptosis, and DNA fragmentation.

Free radical generation by selenium compounds and their prooxidant toxicity.

Selenium (Se) and many of its compounds are among the most toxic of nutrients. Selenium toxicity was first described in range animals in the western United States in the 1930's which consumed "selenium accumulator" plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya. Selenites and selenates from the soil accumulate in these plants primarily as methylated selenium compounds and plants evolve dimethyldiselenide and dimethylselenide. Dietary selenium, primarily as selenomethionine and selenocysteine for humans fulfill the dietary requirement for selenoenzymes and proteins. In humans and animals excessive dietary selenium may be toxic. In vitro, selenium compounds such as selenite, selenium dioxide and diselenides react with thiols, such as glutathione, producing superoxide and other reactive oxygen species. This catalytic reaction of selenium compounds with thiols likely accounts for selenium toxicity to cells ex vivo and in vivo where the major glutathione producing organ, the liver, is also the major target organ of selenium toxicity. Selenium enzymes and selenoethers that do not readily form a selenide (RSe-) anion and compounds such as Ebselen where selenium is sequestered, are not toxic. Methylation of selenium by both plants and animals serves to detoxify selenium by generating methylselenides. Alternatively, full reduction of Se to elemental selenium (Se0) as done by some bacteria and the formation of heavy metal selenides such as Ag2Se or Hg2Se, results in a non-catalytic non-toxic form of selenium. This catalytic prooxidant attribute of some selenium compounds appears to account for its toxicity when such activity exceeds plant and animal methylation reactions and antioxidant defenses. This prooxidant activity may also account for cellular apoptosis and may provide a useful pharmaceutical application for selenium compounds as antibacterial, antiviral, antifungal and anticancer agents.

Bioavailability of selenium from veal, chicken, beef, pork, lamb, flounder, tuna, selenomethionine, and sodium selenite assessed in selenium-deficient rats.

The bioavailability of selenium (Se) from veal, chicken, beef, pork, lamb, flounder, tuna, selenomethionine (SeMet), and sodium selenite was assessed in Se-deficient Fischer-344 rats. Se as veal, chicken, beef, pork, lamb, flounder, tuna, SeMet, and sodium selenite was added to torula yeast (TY) basal diets to comprise Se-inadequate (0.05 mg Se/kg) diets. Se as sodium selenite was added to a TY basal diet to comprise a Se-adequate (0.10 mg Se/kg), Se-control diet. The experimental diets were fed to weanling Fischer-344 rats that had been subjected to dietary Se depletion for 6 wk. After 9 wk of the dietary Se repletion, relative activity of liver glutathione peroxidase (GSHPx) from the different dietary groups compared with control rats (100%) was: flounder 106%, tuna 101%, pork 86%, sodium selenite 81%, SeMet 80%, beef 80%, chicken 77%, veal 77%, and lamb 58%. Se from flounder was the most efficient at restoring Se concentrations in the liver and skeletal muscle. Se from sodium selenite, SeMet, beef, veal, chicken, pork, lamb, and tuna was not dietarily sufficient to restore liver and muscle Se after 9 wk of recovery following a 6-wk period of Se depletion.

Severe dietary magnesium deficiency does not alter levels and function of myocardial Gs alpha and Gi alpha.

Magnesium ions (Mg2+) play a crucial role in the activation and synthesis of guanine nucleotide-binding proteins (G proteins). However, there is no information about the influence of in vivo magnesium deficiency on the function and levels of G proteins. This study was done to investigate whether dietary magnesium deficiency alters function and levels of the two major myocardial G proteins, Gi alpha and Gs alpha. Severe hypomagnesemia and a significant reduction of myocardial magnesium occurred in rats fed a magnesium-deficient diet for 6 wk vs. rats fed a normal-magnesium diet (control). The magnesium-deficient rats developed focal myocardial lesions but their cardiac function was not impaired. Myocardial immunodetectable Gs alpha and Gi alpha levels of magnesium-deficient rats did not differ from control (Gs alpha: 2.39 +/- 0.52 vs. 2.76 +/- 0.72 arbitrary units/microgram protein, P > 0.05; Gi alpha: 1.60 +/- 0.52 vs. 1.89 +/- 0.30 arbitrary units/microgram protein, P > 0.05). Similarly, the function of Gs alpha and Gi alpha estimated by basal and ligand-stimulated adenylyl cyclase activity was not significantly different between the two groups of animals. The results show that dietary-derived magnesium deficiency sufficient to produce severe hypomagnesemia does not produce any significant change in levels or function of myocardial G proteins.

Inhibition of selenite-catalyzed superoxide generation and formation of elemental selenium (Se(o)) by copper, zinc, and aurintricarboxylic acid (ATA).

Selenite catalyzes the oxidation of glutathione (GSH) with the subsequent generation of superoxide (O2.-). Copper, zinc, and aurintricarboxylic acid (ATA) were tested for their ability to inhibit both the selenite-catalyzed generation of superoxide and the conversion of selenite to elemental selenium (Se(o)). As measured by lucigenin-dependent chemiluminescence (CL), copper, zinc, and ATA were shown to inhibit significantly (P < 0.05) selenite-catalyzed CL in a concentration-dependent manner. The inhibition of the selenium-catalyzed generation of superoxide by copper(II) was greater than by either zinc or ATA. In addition, Copper, zinc, and ATA all inhibited the conversion of selenite to Se(o). Inhibition of selenite-catalyzed CL by copper, zinc, and ATA is believed to occur as the result of inhibition of Se2- and/or GSSe-, the catalytic selenopersulfide anion of GSH.

Cytolysis of human erythrocytes by a covalent antibody-selenium immunoconjugate.

A selenium (Se)-containing immunoconjugate of a human anti-erythrocyte membrane antibody (Ab-Se) has been synthesized via oxidation of the carbohydrate moieties of the antibody and covalent coupling with selenocystamine. The isolated Ab-Se immunoconjugate is shown to be more hemolytic than is selenocystamine when expressed on equivalent selenium basis. Native antibody preincubated with the human erythrocytes prevented hemolysis induced by the Ab-Se immunoconjugate. As observed microscopically, the Ab-Se immunoconjugate caused extensive damage to the erythrocyte membrane and lysis. The cytotoxicity of Se toward the human erythrocytes is believed to be caused initially by the localized generation of superoxide (O2.-) within the cell membrane. This is the first demonstration of site-directed immunoselectivity of Se cytotoxicity and demonstrates the potential for a free radical pharmacology based on localized Se-generated O2.-.

Dietary magnesium deficiency increases Gi alpha levels in the rat heart after myocardial infarction.

OBJECTIVE: Magnesium (Mg) is crucial for the function of G proteins which play important roles in mediating the inotropic effects of beta adrenergic agonists in the heart and are altered in heart failure. This study was performed to determine whether or not dietary Mg deficiency alters functional activity and levels of the two major ventricular G proteins, Gi alpha and Gs alpha in the heart after myocardial infarction (MI). METHODS: Six week old rats were fed an Mg adequate or deficient diet for 6 weeks. At the end of week 3, MI was induced by coronary artery ligation. A sham operation was performed as control. After surgery, surviving animals were maintained on their assigned diets for another 3 weeks. Then, cardiac function was measured, plasma and tissue were collected. RESULTS: Severe hypomagnesemia and increased plasma catecholamine level were observed in all animals fed the Mg deficient diet. A significant reduction of myocardial Mg concentration accompanied by elevated plasma and myocardial calcium concentrations was observed in MI animals with existing Mg deficiency vs. animals fed the Mg adequate diet. Cardiac function was impaired in MI rats and further reduced in MI rats with existing Mg deficiency. Gi alpha level was not altered by either Mg deficiency or MI alone, but was dramatically elevated in animals with combined Mg deficiency and MI (9.9 +/- 0.7 arbitrary unit.mg-1 protein) as compared to MI alone (5.8 +/- 0.6, P < 0.05) and Mg deficiency alone (6.1 +/- 0.8, P < 0.05). Gs alpha level did not differ between groups. GppNHp-, but not fluoride-stimulated adenylyl cyclase activity was slightly reduced in MI animals with existing Mg deficiency. CONCLUSION: The findings suggest that dietary Mg deficiency increases the expression of Gi alpha in the heart after MI, while levels and function of Gs alpha are not compromised during dietary Mg deficiency either with or without MI.

Dynamic changes in G alpha i-2 levels in rat hearts associated with impaired heart function after myocardial infarction.

The objective of this study was to determine if levels and function of Gs alpha and G alpha i-2 in rat hearts change over time following acute myocardial infarction (MI), and if so, whether the changes in G proteins are associated with changes in heart function. As compared with sham-operated controls, the G alpha i-2 level of MI rats did not change at day 1, increased by 64% at day 3 (P < 0.01) and by 55% at day 9 (P < 0.05) accompanied by reduced adenylyl cyclase activity, and returned to control by day 21. By contrast, the Gs alpha level did not change at any time. Cardiac function in MI animals was markedly impaired at days 1, 3, and 9 as evidenced by substantial elevation in LVEDP and reduction in maximum rates of pressure development and relaxation, and was partially restored at day 21. Increased G alpha i-2 level in MI rats correlated significantly to severity of impaired cardiac function. The results show a three-phase dynamic pattern in G alpha i-2 level following acute MI: a lag phase, an increased expression phase associated with marked impairment of heart function, and a late phase in which the expression returns to control level accompanied by partially restored cardiac function.

Selenium from beef is highly bioavailable as assessed by liver glutathione peroxidase (EC 1.11.1.9) activity and tissue selenium.

The bioavailability of Se from ground beef has been previously found in this laboratory to be greater than that of selenite or selenate when fed to female Fischer 344 rats. In the present study we examined the bioavailability of Se from various commercial portions of beef, the liver, striploin, round, shoulder and brisket. All beef was cooked, freeze-dried, finely powdered and mixed with the other dietary ingredients. The experimental diets were fed to the weanling Fischer 344 rats which had been subjected to dietary depletion of Se for 6 weeks. The bioavailability of Se from the beef diets was compared with that of Se as selenite or L-selenomethionine (SeMet) added to torula-yeast diets. Each experimental diet contained 0.10 mg Se/kg. After 8 weeks of dietary Se repletion, relative activity of liver glutathione peroxidase (EC 1.11.1.9; GSHPx) from the different dietary groups compared with that of control animals (100%) was (%): selenite 91, SeMet 122 (P < 0.05), liver 108, striploin 105, round 106, shoulder 106, brisket 103. Se recovery for liver GSHPx was generally highest from SeMet > beef muscle = beef liver > selenite. Muscle tissue deposition of Se was highest from SeMet > beef muscle > selenite = beef liver. In addition, the faecal excretion of Se was lowest from the SeMet dietary group and highest from the selenite dietary group. The experimental results suggest that all cuts of beef appear to be highly bioavailable sources of dietary Se when compared with selenite or L-SeMet.

On the nature of selenium toxicity and carcinostatic activity.

Selenium toxicity was first confirmed in 1933 to occur in livestock that consumed plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya in the western regions of the United States. In 1957 selenium was identified as an essential nutrient for laboratory rats and soon thereafter for chickens and sheep. Essentiality for mammalian species was established in 1973 with the discovery that the enzyme glutathione peroxidase contained selenium. During this same period of time, human epidemiological evidence suggested that selenium possessed anticarcinogenic effects. Since the 1970s, many animal studies have confirmed the human epidemiologic evidence that selenium compounds possess carcinostatic activity. Less progress has been made in explaining why many of these compounds of selenium are toxic and why these same compounds are carcinostatic. In 1988 the observation was made that oxidation of glutathione by selenite produced superoxide, opening a new area for selenium research. This present paper, drawing information from the literature on selenium metabolism in plants and animals, selenium toxicology, selenium cytotoxicity, and selenium carcinostatic activity in animals over the last sixty years, sets forth a probable biochemical catalytic mechanism that encompasses both selenium toxicity and selenium carcinostatic activity. The thesis presented here for scrutiny is that compounds of selenium are toxic owing to their prooxidant catalytic activity to produce superoxide (O2.-), hydrogen peroxide, and very likely other cascading oxyradicals. The toxicity of selenium compounds is countered by plant and animal methylation reactions and antioxidant defenses. As carcinostasis is mostly known to occur at supranutritional levels of selenium in animals, carcinostasis appears to be directly correlated to selenium toxicity. The catalytic toxic selenium specie appears to be the metabolic selenide (RSe-) anion.

Bioavailability of selenium from raw and cooked ground beef assessed in selenium-deficient Fischer rats.

OBJECTIVE: The literature on the bioavailability of selenium (Se) from meats, especially beef, is meager, and that which existed when this research began suggested that Se was not highly bioavailable. In addition, much of the analytical values for Se in beef predated the Food and Drug Administration's 1973 approval of Se as an additive to feeds and mineral premixes of livestock. DESIGN: One hundred and thirty-six weanling female Fischer 344 rats were divided into two dietary groups: the selenium deficient group in which animals were fed a torula yeast (TY) basal diet which contained 0.008 mg/kg Se and the control group in which animals were fed the TY diet to which was added 0.10 mg/kg Se as sodium selenite. RESULTS: After 6 weeks of dietary treatment liver glutathione peroxidase (GSHPx) activity had fallen in the Se-deficient rats to 2.4% of that of control rats. At this time (week 6) rats from the Se-deficient TY diet were refed diets containing 0.10 mg/kg Se as selenite, selenate, raw or cooked ground beef that had been freeze-dried. During the Se-repletion period rats were sacrificed at weeks 1, 3, 5 and 8. Liver GSHPx activity and total Se levels in liver and muscle tissue were the criteria of Se bioavailability. After 8 weeks of Se resupplementation the recovery of liver GSHPx activity compared to the control animals (set at 100%) were selenite (98%, p > 0.05), selenate (117%, p < 0.05), raw beef (127%, p < 0.05) and cooked ground beef (139%, p < 0.05). Total Se in both liver and muscle tissue reflected the liver GSHPx activity with the total Se concentration in tissues being highest for cooked beef. CONCLUSION: The data suggest that bioavailability of Se from ground beef is greater than that from either selenite or selenate.

The selenium content of selected meats, seafoods, and vegetables from Lubbock, Texas.

The selenium content of some frequently consumed foods from a commercial beef packer, a road-side vendor, and local stores in Lubbock, Texas was determined and compared to selenium data for the same or similar foods in the United States and from other countries. The comparative content of selenium in foods covered the period of time between 1970 and 1993. Our selenium analyses of foods show that on a fresh weight basis, the selenium content of seafoods > commercial beef > pork > ground beef > chicken. Cooking, air- or freeze-drying increased the selenium content of all foods significantly. When the selenium content of local foods is compared to similar foods in the United States and other countries, with few exceptions, there exists great uniformity in the selenium content in the major food groups, meats, fish, milk, and vegetables. New Zealand, known for its low soil selenium, had the lowest comparative food selenium content.

Generation of reactive oxygen species from the reaction of selenium compounds with thiols and mammary tumor cells.

Sodium selenite, sodium selenate, selenocystine and selenomethionine were tested for their abilities to generate superoxide by the oxidation of glutathione and other thiols in the absence and presence of cells of the human mammary tumor cell line HTB123/DU4475. Free radical generation was measured by lucigenin- or luminol-amplified chemiluminescence. In the absence of tumor cells, lucigenin-dependent chemiluminescence was observed from the reaction of selenite with the thiols glutathione, 2-mercaptoethanol and L-cysteine, but not with oxidized glutathione. Superoxide dismutase, catalase, and glutathione peroxidase all suppressed the observed chemiluminescence; but when these enzymes were heat inactivated they had little suppressive inhibition on chemiluminescence. Luminol-dependent chemiluminescence from the reaction of selenite with glutathione was much less than that observed by lucigenin-amplified chemiluminescence. In the presence of the HTB123/DU4475 mammary tumor cells, lucigenin-dependent chemiluminescence was observed from the reactions of selenite and selenocystine with glutathione which were 5 and 23 times greater than their respective reactions with glutathione in the absence of tumor cells. The enhanced chemiluminescence generated by selenite and selenocystine in the presence of the tumor cells was also suppressed by superoxide dismutase, catalase and glutathione peroxidase. These data suggest that a free radical, the superoxide anion (O2-), and H2O2 are produced from the reaction of selenite and selenocystine with glutathione. These free radical reactions may account for the toxicity of selenite and selenocystine in vitro in comparison to a near absence of acute tumor cell toxicity and superoxide generation by selenate and selenomethionine with thiols. Enhanced chemiluminescence in the presence of tumor cells may be an expression of cellular selenium metabolism and the capability of cells to form selenium metabolites that more easily oxidize glutathione and other thiols producing reactive free radicals and peroxides.

Effect of selenium compounds and thiols on human mammary tumor cells.

The effect on cell viability and growth rate of sodium selenite, selenocystine, sodium selenate, and selenomethionine at selenium concentrations of 6.25 and 12.5 uM was studied in vitro on cells of the human mammary tumor cell line HTB123/DU4475. Selenite and selenocystine affected both cell viability and growth rate of the tumor cells at these selenium concentrations. Selenite and selenocystine decreased intracellular glutathione concentrations, but did not affect tumor cell glutathione peroxidase activity. After six days of exposure to either selenate or selenomethionine, the viability of tumor cells remained stable, but cell growth, as measured by numbers of cells, was retarded. Neither selenate nor selenomethionine produced changes in concentrations of intracellular glutathione. The toxic effect of selenite on tumor cells was enhanced by addition of 0.25 mM glutathione to the growth medium. Preincubation of the tumor cells with 62.5 uM buthionine sulfoximine decreased cellular glutathione to 15% of controls at 24 h and enhanced the toxicity of selenite toward the tumor cells. Glutathione, 2-mercaptoethanol, and L-cysteine were all toxic to the tumor cells in a dose-dependent manner.

Effect of dietary selenium and magnesium on human mammary tumor growth in athymic nude mice.

The effect of dietary selenium (Se) supplementation and low dietary magnesium (Mg) on growth of cells of the human mammary tumor cell line (HTB123/DU4475) and the tissue glutathione (GSH) content in female athymic nude mice was studied. Sixty three- to four-week-old female athymic nude mice were randomly divided into six dietary groups of 10 animals. The mice were fed a modified AIN-76A diet with two levels of Mg (100 and 665 mg/kg) and three levels of Se (0.04, 0.2, and 4.0 mg/kg). At the fourth week of dietary treatment, mice were subcutaneously inoculated with 2.5 x 10(6) viable tumor cells on the dorsal lumbar region and then fed their respective diets for another four weeks. Dietary Se supplementation had no significant effect on tumor growth or tissue GSH content. Low dietary Mg limited both tumor growth and tissue GSH synthesis but raised Mg and GSH levels in tumor tissues. The growth of mice fed the diet containing 100 mg/kg Mg and 4.0 mg/kg Se was significantly retarded. This study demonstrated that neither Se deficiency nor Se supplementation had any effect on mammary tumor growth or tissue GSH content in athymic nude mice. Low dietary Mg did retard tumor growth and inhibited GSH synthesis. Low dietary Mg also resulted in an apparent increase in Se toxicity in these animals.

In vitro evidence for a relationship between magnesium and vitamin B-6.

Vitamin B-6 and magnesium appear to interact in vivo and it has been suggested that vitamin B-6 may enhance transport or accumulation of magnesium in cells. The purpose of this study was to evaluate the possibility of the formation of B-6 vitamer-Mg complexes in vitro using spectrophotometric analysis of ultraviolet or visible spectra or change in fluorescence intensity of B-6 vitamers. Pyridoxal phosphate but not pyridoxal appears to form a complex with Mg as evidenced by a change in the ultraviolet and visible spectra with an increase in absorption and spectral shift in the visible maxima from 389 to 388 nm and a decrease in the ultraviolet absorption maxima at 296 nm. Addition of Mg to pyridoxal phosphate but not the other B-6 vitamers enhanced the fluorescent intensity of pyridoxal phosphate at least threefold and evoked a spectral shift in both the fluorescence excitation and emission maximum. Electrochemical titration of pyridoxal phosphate in the presence of Mg affects the pKa- of the phenolic hydroxyl and the secondary phosphate ionization. These data collectively indicate that pyridoxal phosphate, but not pyridoxal, appears to form a coordinated complex with Mg and the coordination site is likely to be related to the primary phosphate and aldehyde moiety of pyridoxal phosphate.