Selenium in maternal and infant nutrition.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
J A Milner
Publications and source records attributed to J A Milner.
Metabolic aberrations associated with arginine deficiency.
The significance of dietary arginine deficiency is often unrecognized since growth and nitrogen balance are generally positive. However, inadequate intakes of dietary arginine are typically associated with dramatic alterations in intermediary metabolism in mammals. Most of the symptoms that develop following arginine deprivation can largely be accounted for by a decreased efficiency of ammonia detoxification. However, species differences in the metabolic aberrations associated with arginine deficiency are clearly evident. Therefore, selected animals fed an arginine-deficient diet may serve as a useful model for the study of chronic hyperammonemia. In rats, mice, hamsters, guinea pigs and rabbits, the excretion of citric and orotic acid is a sensitive indicator of arginine availability. Increased orotic acid production is reduced or prevented by inclusion of the urea cycle intermediates arginine, citrulline or ornithine. However, growth in the rat is stimulated only when arginine or citrulline are included in the diet. Increased orotic biosynthesis is observed with increasing ammonia concentrations in rat, mouse and human liver and is reduced by in vitro arginine supplementation. The fatty infiltration of the rat fed an arginine-deficient diet is associated with changes in the ratio of purine to pyrimidine bases and is corrected by the dietary addition of adenine. The arginine-deficient rat should serve as a model for examining the dynamic interrelationship of the urea cycle with pyrimidine and purine biosynthesis.
Ammonia↗
Selective effects of selenium selenite on 7,12-dimethylbenz(a)anthracene-DNA binding in fetal mouse cell cultures.
Sodium selenite inhibits the binding of 7,12-dimethylbenz(a)anthracene (DMBA) to DNA in tertiary cultures of fetal mouse cells in a rather selective fashion. Inhibition can be demonstrated at 6 but not at 3 h after DMBA addition to the cells. Inhibition is seen after treatment of the cells with DMBA concentrations of 0.05 or 0.1 micrograms/ml but not after treatment at 0.01 micrograms/ml. Furthermore the inhibition seen with up to 1 microgram selenium/ml is selective in that products from the anti bay region dihydrodiol epoxide metabolite (where the epoxide oxygen is trans to the 4-hydroxy group) are suppressed while those from the syn-dihydrodiol-epoxide (where the epoxide oxygen is cis to the 4-hydroxy group) are not affected. In the absence of selenite, it was found that syn-dihydrodiol epoxide-DNA adducts are formed in a roughly linear fashion with time over a range of DMBA concentration. In contrast, the capacity of the cells to generate anti-dihydrodiol-epoxide adducts in a 3-h interval is saturated at concentrations of DMBA above 0.025 micrograms/ml and after the initial 3-h period the cells generate these adducts at up to a 6-fold greater rate than during the initial 3 h. This increase in rate of formation of anti-dihydrodiol-epoxide products is inhibited by actinomycin D and appears to be a consequence of DMBA inducing an enzyme activity which selectively generates the anti-dihydrodiol-epoxide and not the syn-dihydrodiol-epoxide. The selective action of sodium selenite in inhibiting only anti-dihydrodiol-epoxide product formation and doing this only at certain times and at certain doses of DMBA is a result of the fact that it inhibits the induction process. Once induction has occurred, sodium selenite is no longer inhibitory of DMBA-DNA binding. The chemopreventive action of selenium in chemical carcinogenesis could be partially attributable to effects such as those described herein on carcinogen-DNA binding. It is also possible, however, that the chemopreventive actions of selenium might be attributable to effects on the expression of genes other than those involved in carcinogen metabolism.
9,10-Dimethyl-1,2-benzanthracene↗
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.
Animals↗
Effect of dietary protein concentration on rat-liver S9 bioactivation of 7,12-dimethylbenz[a]anthracene in the Salmonella/microsome assay.
These studies describe the influence of dietary protein concentration on the ability of rat-liver postmitochondrial fraction (S9) to mediate 7,12-dimethylbenz[a]anthracene (DMBA) mutagenicity in the Ames Salmonella/microsome assay. A negative correlation was observed between dietary protein content and DMBA mutagenicity. The effect of protein was not dependent on the quantity of Aroclor used for induction. Dietary protein did not influence the mutagenicity of DMBA when isolated microsomes were used in place of S9.
9,10-Dimethyl-1,2-benzanthracene↗
Inhibition of human breast cancer cells by selenium.
The viability of human breast cancer cells (cell lines MCF-7 and MDA-MB 231) was inhibited in vitro in a dose-dependent manner by selenium supplementation. However, a normal diploid human cell line (MRC-5) was relatively resistant to selenium supplementation. The presence of selenium as Na2SeO3 at 1.1 X 10(-6) M reduced cancer cell viability by approximately 50%, whereas non-cancerous cells were not affected. Parenteral administration of sodium selenite also significantly inhibited the growth of the cancerous cell lines transplanted into nude mice. Selenium administration at 0.8 micrograms/g body wt resulted in an 80-93% reduction in the rate of tumor growth without apparent ill effects on the host.
Animals↗
Effect of arginine on the carcinogenicity of 7,12-dimethylbenz[a]-anthracene and N-methyl-N-nitrosourea.
The effects of supplementing a 14% casein diet with 5% L-arginine on rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea (MNU) were investigated. Dietary arginine supplementation had no significant effect on food intake or growth. In rats treated with either DMBA or MNU, tumor incidence was not significantly affected, but the number of new tumors appearing each week and the cumulative tumor weight per rat were significantly decreased in rats fed 5% arginine diets. In vitro experiments indicated that arginine had no effect on the enzymatic conversion of DMBA to electrophilic DNA-binding metabolites. The decreased tumorigenicity of both MNU and DMBA in rats given supplemental arginine suggests that this amino acid has an inhibitory effect on stage(s) of chemical carcinogenesis other than bioactivation of procarcinogens.
9,10-Dimethyl-1,2-benzanthracene↗
Dietary arginine deprivation and delayed puberty in the female rat.
Dietary arginine deprivation was found to delay puberty in the female rat. Physiological pinealectomy by exposing to constant light suggests this gland is not involved in this delay. Compensatory ovarian hypertrophy (COH) was used to test the hypothalamic sensitivity to negative steroid feedback. COH occurred in hemiovariectomized immature rats ad libitum fed the control or arginine-deficient diet but failed to occur in hemiovariectomized, underfed, growth-matched control rats, which suggests that feed restriction and arginine deficiency do not exert identical effects on the hypothalamic-pituitary-gonadal axis. Puberty, as defined by vaginal opening, first ovulation and the initiation of estrous cycles, was advanced by a week in the immature female rat fed a control diet after treatment with estradiol benzoate, 0.05 microgram/(100 g body weight X day) starting at 26 days of age. The time of first estrus and the first ovulation was not advanced in arginine-deficient rats by the same dosage of estrogen when administration began at 26 days of age. Treatment at an older age (40 or 54 days) or with a higher dosage [0.25 microgram/(100 g body weight X day)] at 26 days of age did advance puberty. The failure of estrogen to induce a vaginal cyclicity suggests an insufficient amount of endogenous estrogen to trigger a gonadotropin surge to cause the onset of puberty in the rat fed an arginine-deficient diet.
Animals↗
Leucine, isoleucine and valine requirements of immature beagle dogs.
Three experiments were conducted with growing beagle dogs fed crystalline L-amino acid diets, to determine the requirement for each of the branched-chain amino acids: leucine, isoleucine and valine. Requirements were taken as the minimum dietary concentrations required for optimal growth, feed efficiency and nitrogen retention. For each amino acid, the requirements estimated from each of these criteria were similar. Ten- to 12-week-old male beagle dogs were found to require 0.65% leucine, 0.40% isoleucine and 0.43% valine. These values correspond to 159 mg leucine, 98 mg isoleucine and 105 mg valine per 100 kcal dietary metabolizable energy. These branched-chain amino acid requirements of the growing dog are lower than those of weanling rats or pigs.
Animals↗
Phenylalanine and tyrosine requirements of immature beagle dogs.
Experiments were conducted with immature Beagle dogs to determine the dietary requirement for phenylalanine. With purified L-amino acid diets the requirement for this aromatic amino acid to optimize growth, feed efficiency and nitrogen balance was found to be 0.8%. Dietary limitations in the quantity of phenylalanine resulted in an increase in plasma and urinary urea. Breakpoint analysis of plasma phenylalanine concentrations also indicated a dietary requirement of 0.8%. The present data indicate that the dietary requirement for phenylalanine can be met by supplying approximately 195 mg per 100 kcal metabolizable energy or 518 mg per kilogram body weight per day. In a separate study, tyrosine was found to meet approximately 46% of the phenylalanine requirement of the immature dog. Consumption of diets containing tyrosine in the presence of optimal phenylalanine did not further stimulate growth, feed efficiency or nitrogen balance.
Administration, Oral↗
Species comparison of the influence of ammonia on orotic acid and urea biosynthesis in liver.
Although orotic aciduria occurs in both male and female rats fed an arginine-deficient diet, only hepatocytes from male rats exhibited an enhanced rate of orotate biosynthesis to increasing ammonium compared to controls. Inhibition of incorporation [14C]NaHCO3 into urea by norvaline in the rat and mouse was accompanied by a 20 and 25% increase in orotate biosynthesis, respectively. Injection of ammonium chloride (2 mmol/kg) or consumption of a diet devoid of arginine resulted in an increased urinary orotate excretion in the rat. Injection of a similar quantity of ammonium chloride in mice did not result in an orotic aciduria. The influence of ammonia and arginine on the biosynthesis of orotic acid and urea in isolated liver slices from various mammals was also examined. In rat, mouse and pig liver, increasing quantities of ammonia stimulated the incorporation of [14C]NaHCO3 into orotic acid. In porcine, bovine and ovine liver the incorporation of [14C]NaHCO3 into orotic acid was low and was minimally effected by supplemental ammonia. Addition of arginine to the incubation medium diminished the incorporation of [14C]NaHCO3 into orotic acid in the liver of all species examined except the cow and sheep. This decrease was accompanied by a stimulation of urea biosynthesis in the rat, but a depression in the pig. Addition of ammonium (5.0 mM) markedly increased the incorporation of [14C]NaHCO3 into urea in all mammalian liver slices examined. These studies show that the liver of various mammals can respond to increasing ammonia by increasing orotic acid biosynthesis. However, species differences in the response to ammonia are evident.
Ammonia↗
Factors influencing the antitumorigenic properties of selenium in mice.
Sodium selenite (Na2SeO3) was administered at 2.0 micrograms selenium (Se) to Swiss ICR mice six times over a 9-day period by intraperitoneal (i.p.) injection or by gastric gavage. Survival time was significantly increased in Ehrlich ascites tumor (EAT)-bearing mice by 170 and 20%, respectively, compared to controls. In two separate studies, 5.0 micrograms Se as Na2SeO3 or selenodiglutathione (GSSeSG) administered i.p. was more effective in inhibiting EAT propagation in mice than either untreated (control) mice or mice receiving sodium selenide, dimethyl selenide [(CH3)2Se] or seleno-DL-cystine. In another study, EAT cells were preincubated with either 1 or 3 ppm Se as GSSeSG, Na2SeO3, or (CH3)2Se, washed, and reinoculated into mice. Only in mice inoculated with cells pretreated with GSSeSG was a significant increase in survival observed. The observed tumor inhibition was not limited to ascitic tumors since growth of solid Ehrlich tumors was also significantly inhibited by i.p. treatment of Na2SeO3. Following i.p. administration of Na2(75)SeO3, the solid tumors retained more selenium-75 than did blood, lung, kidney, or liver. Supplementation of a torula yeast diet with 2.5 or 5.0 ppm Se as Na2SeO3 also significantly increased the survival time of EAT-bearing mice. These data show that the form and mode of administration of selenium influence the antitumorigenic properties of this trace element. In addition, the data suggest that some intermediate in the normal pathway for selenium detoxification is probably responsible for this trace element's antitumorigenic properties.
Animals↗
The effects of dietary selenium on the biotransformation of 7,21-dimethylbenz[a]anthracene.
The influence of dietary selenium on the mutagenic activation of 7,12-dimethylbenz[a]anthracene (DMBA) by rat liver S9 was studied using the Ames test. Rats received supplemental selenium, as sodium selenite, in the drinking water or in the diet. All rats additionally received 0, 20, 50, 100, or 500 mg Aroclor 1254 per kg body weight. Revertant counts decreased 72 and 31% at the 20- and 100-mg/kg induction levels, respectively, with S9 preparations from rats given selenium supplementation, compared to controls. No significant effects of selenium on S9 preparations was observed in rats treated with 500 mg/kg Aroclor. Preparations of S9 from rats receiving 2.5 ppm Se in their diet produced 46, 84 and 70% less revertants than controls at the 20-, 50- and 100-mg/kg induction levels. Increasing the selenium concentration in the diet to 5 ppm reduced the revertant counts by 71, 68 and 65%, at the 20-, 50- and 100-mg/kg induction level of Aroclor, respectively. Dietary selenium supplementation was shown to decrease the mutagenic activation of DMBA by liver microsomes. These studies indicate that in vivo selenium supplementation may reduce susceptibility to the action of various carcinogens.
9,10-Dimethyl-1,2-benzanthracene↗
Effect of selenium on growth rate of canine mammary carcinoma cells in athymic nude mice.
A canine mammary tumor cell line established from a carcinoma of the solid type was used in this study. In 2 separate experiments, athymic nude mice were inoculated subcutaneously with 5 x 10(6) viable tumor cells. All tumor-bearing mice received subcutaneous injections thrice weekly of 2 micrograms/g body wt of selenium as sodium selenite or phosphate buffered saline. Control, non-tumor-bearing mice were injected with either selenium or buffer. Selenium administration did not significantly alter the growth of non-tumor-bearing mice. However, body weight of tumor-bearing mice was reduced approximately 10%. The average volume of tumors in selenium treated mice was reduced 76% in experiment I and 74% in experiment II.
Animals↗
Selenium intakes and status of human milk and formula fed infants.
Selenium status was assessed in 28 infants receiving either human milk (n = 8) or a proprietary formula (n = 20) as their sole nutritional source from birth to 3 months. Infants' selenium intakes were determined from dietary records, "test weighings," and direct analysis of human milk and formula. Fore milk samples (n = 72) collected from group I mothers had a mean selenium concentration (ng/ml) of 16.3 +/- 4.9, whereas the selenium content of proprietary formula was 8.6 +/- 0.9. The selenium concentration of hind milk was significantly greater (p less than 0.05) than that of fore milk. At 3-months selenium intakes as well as serum selenium concentrations for human milk fed infants were significantly greater than those for formula fed infants. A significant positive correlation (r = 0.42; p less than 0.05) was found between infants' selenium intakes and their serum selenium concentrations. The results indicate that feeding practice directly affects selenium status during infancy.
Animals↗
Effect of arginine deficiency on mammary gland development in the rat.
The effect of dietary arginine deficiency on rat mammary gland development was investigated in pregnant rats and ovariectomized nonpregnant rats. Consumption of an arginine-deficient diet from day 0 of pregnancy significantly reduced the total DNA and RNA content of the mammary gland by day 20. Pair-feeding studies revealed that reduced food intake associated with consumption of the arginine-deficient diet was not responsible for the altered nucleic acid content of the gland. Restriction of food intake by pair-feeding did reduce the wet weight of the mammary gland as well as its fat content when compared with ad libitum fed controls, but the degree of reduction did not fully account for the depressing effect on the wet weight and fat content observed when the arginine-deficient diet was fed. The ratio of RNA to DNA in the mammary tissues of rats fed the arginine-deficient diet indicated normal protein synthetic activity per cell. The extent of reduction in mammary nucleic acid content by arginine deficiency was similar for pregnant rats and ovariectomized nonpregnant rats treated with estrogen and progesterone. These studies show that dietary arginine is required for optimal mammary growth. The possible mechanism(s) by which arginine can modify mammary growth are discussed.
Animals↗
Dietary arginine and sexual maturation of the female rat.
The effects of dietary arginine deficiency on sexual maturation were examined in the female rat. Consumption of a diet devoid of arginine since weaning delayed the onset of puberty. Weight at vaginal opening and weight at first estrus were significantly greater in the arginine-deficient rat than in the control rat. Arginine deficiency appeared to have a specific effect on the development of reproductive function since puberty in arginine-deficient animals was delayed more than could be accounted for by impairment of growth. The specific effect of arginine deficiency was also indicated by reduced weights of the reproductive tissues after 15 weeks of experimental feeding when compared with the growth-matched controls. Sexual maturation was also examined in rats fed diets containing graded levels of arginine (1.12, 0.84, 0.56, 0.28 or 0%). Vaginal opening and first estrus were delayed by feeding diets containing 0.28 or 0% arginine. Uncoupling of these two events also occurred in the majority of the rats fed these two diets. In spite of normal timing of puberty, maturing rats fed a diet with 0.56 of 0.84% arginine had reduced ovarian weight and first ovulation rate when compared with rats fed the control diet (1.12% arginine). It is concluded that more than 0.84% dietary arginine was required for growing rats to support normal sexual maturation.
Animals↗
Effects of dietary protein quantity and quality on the growth of dogs and rats.
The growth of immature beagle dogs and weanling rats fed dietary protein concentrations between 0 and 20% were investigated. With lactalbumin as the protein source, 8- to 10-week-old dogs exhibited optimal growth when the diet supplied between 15 and 20% protein, whereas in older growing dogs (13-17 weeks) maximum growth and feed efficiency occurred with 11.7% dietary protein. Growth and feed efficiency of weanling rats were calculated to be optimal at 11.5% dietary protein. The protein efficiency ratio (PER) calculated during 14 days of feeding a 10% lactalbumin diet was 3.14 for 8- and 10-week-old dogs, 3.42 for 13- to 17-week-old dogs and 3.92 for weanling rats. Subsequent experiments examined the utilization of casein, soy isolate and wheat gluten by immature dogs and weanling rats. When diets contained 10% protein the adjusted PERs of casein, soy and wheat gluten were 2.50, 1.26 and -0.43 for the dog and 2.50, 1.60 and 0.34 for the rat, respectively. At 7.5% protein the adjusted PERs of casein, soy and wheat gluten were 2.50, 1.19 and -3.21 for the dog and 2.50, 1.44 and 0.29 for the rat. Thus, the rat can be a useful model for examining the quality of proteins fed to dogs. However, by using the rat one may overestimate the value of some low quality proteins.
Animals↗