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PubMed1992

Chromosomal aberrations and sister-chromatid exchanges induced by N-nitroso-2-acetylaminofluorene and their modifications by arsenite and selenite in Chinese hamster ovary cells.

The frequencies of chromosomal aberrations (CA) and sister-chromatid exchanges (SCE) in Chinese hamster cells were significantly increased by the direct-acting mutagen N-nitroso-2-acetylaminofluorene (N-NO-AAF) at the concentration of 0.1 mM. N-NO-AAF was prepared by nitrosation of the protohepatocarcinogen 2-acetylaminofluorene. The induced CA, which included chromatid breaks, chromatid exchanges, chromosome breaks, and chromosome ring formation were significantly potentiated by the presence of sodium arsenite (10 microM), but not by hydroxyurea (20 mM) or cytosine arabinoside (25 microM). On the other hand, the clastogenic effect of N-NO-AAF was effectively inhibited by sodium selenite (100 microM). Arsenite (10 microM) was shown to be moderately active in CA induction which was partially blocked by the presence of selenite (10 nM). N-Nitroso compounds such as N-nitroso-N-methylurea, N-nitroso-N-ethylurea and N-methyl-N'-nitro-N-nitrosoguanidine were equally or more active in the induction of CA and SCE in CHO cells when compared with N-NO-AAF. The cell cycle was significantly delayed by the intervention of N-NO-AAF.

2-Acetylaminofluorene↗
PubMed1988

Factors involved in the formation and stabilization of cell aggregates obtained from amphibian embryonic explants.

The effect of factors influencing the formation and stability of animal and vegetal aggregates from Xenopus laevis and Ambystoma mexicanum was examined in the light and scanning electron microscopes. At extreme values of pH the surface coat covering the vegetal aggregates is dissolved and dissociation may take place. Animal aggregates are more resistant. At high tonicities vegetal aggregates may be dissociated, and in the animal aggregates the epidermal differentiation is suppressed. In the absence of Ca2+ the vegetal aggregates are dissociated, but the animal aggregates are not affected. The results obtained with the inhibitor selenate and from incorporation experiments indicate that sulfated glycosaminoglycans are involved in the formation of aggregates in both species. Corresponding observations with tunicamycin suggest that even glycoproteins may play a role in aggregate formation, particularly in the vegetal aggregates.

Ambystoma↗
PubMed1992

Biological activities of trimethylselenonium as influenced by arsenite.

The present study was designed to evaluate three biological activities of trimethylselenonium (TMSe+): anticarcinogenicity, toxicity, and nutritional availability. These experiments were carried out in female rats both in the presence and absence of arsenite because arsenite is known to affect selenium metabolism. Supplementation with TMSe+ by itself in the diet, at levels of 20, 40, or 80 ppm Se, did not offer any protection against mammary carcinogenesis induced by dimethylbenz(a)anthracene. On the other hand, the coadministration of arsenite (5 ppm As) with the two higher levels of TMSe+ resulted in significant tumor suppression. In the acute toxicity experiment, rats were injected subcutaneously with 0.5 or 1 mg Se/kg, preceded 15 minutes earlier by arsenite at doses of 0.5, 1, or 2 mg As/kg. Although treatment with TMSe+ or arsenite alone did not produce any sign of toxicity, a synergistic toxic effect was evident with the combination. Regarding the ability of TMSe+ to restore hepatic glutathione peroxidase following selenium depletion, it was found that a dietary level of 40 ppm Se was necessary for complete recovery. The nutritional biopotency of TMSe+ was not sensitive to either up- or down-regulation by arsenite under conditions where arsenite also enhanced the anticarcinogenic activity of TMSe+. The contrasting effects of arsenite on these two end points suggest that different forms of selenium are involved. It is hypothesized that arsenite might increase the production of a critical metabolite from methylated selenides. However, there is no clear evidence at the present time to suggest whether the same intermediate(s) is responsible for both anticarcinogenicity and toxicity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Selenium inhibition of benzo[a]pyrene, 3-methylcholanthrene, and 3-methylcholanthrylene mutagenicity in Salmonella typhimurium strains TA98 and TA100.

Selenium (Se) decreased the mutagenicity of benzo[a]pyrene (BP), 3-methylcholanthrene (3MC), and 3-methylcholanthrylene (3MCE) in Salmonella typhimurium strains TA98 and TA100. Metabolism of BP, 3MC and 3MCE to mutagens was accomplished with the liver S9 fraction from Aroclor 1254-treated male Sprague-Dawley rats. Exposure of the bacteria to 4 nmoles BP, 10 nmoles 3MC, or 10 nmoles 3MCE in the presence of S9, and up to 200 nmoles Se as Na2SeO3 resulted in decreased mutagenicities up to 39, 66 and 60% of their respective control activities without Se in TA98 and up to 46, 52 and 64% of their respective control activities without Se in TA100. Se (200 nmoles) alone was not mutagenic in strains TA98 or TA100 with or without S9. BP, 3MC and 3MCE were not mutagenic in either strain without S9. None of the tested concentrations of BP, 3MC, 3MCE and Se were cytotoxic. Assays of the aryl hydrocarbon hydroxylase (AHH) activity in the S9 preparation revealed decreased AHH activity with increase in Se concentration. The decreased mutagenicity and AHH activity were Se (as Na2SeO3) dependent and could not be duplicated by sulfur (S as Na2SO3). Inhibition of AHH activity by Se provides an explanation of the mechanism of Se inhibition of BP, 3MC and 3MCE mutagenicities in S. typhimurium TA98 and TA100.

Animals↗
PubMed1987

Biochemical characterization of a thialysine-resistant clone of CHO cells.

The intracellular transport and the activation of lysine, thialysine and selenalysine have been investigated in a thialysine-resistant CHO cell mutant strain in comparison with the parental strain. The cationic amino acid transport system responsible for the transport of these 3 amino acids shows no differences between the 2 strains as regards its affinity for each of these amino acids. On the other hand the Vmax of the transport system in the mutant is about double that in the parental strain. The lysyl-tRNA synthetase, assayed both as ATP = PPi exchange reaction and lysyl-tRNA synthesis, shows a lower affinity for thialysine and selenalysine than for lysine in both strains; in the mutant, however, the difference is even greater. Thus the thialysine resistance of the mutant is mainly due to the properties of its lysyl-tRNA synthetase, which shows a greater difference of the affinities for lysine and thialysine with respect to the parental strain.

Adenosine Triphosphate↗
PubMed1993

A randomized, double-blind, placebo-controlled trial of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo in the treatment of moderate to severe dandruff.

BACKGROUND: Ketoconazole is highly effective against the yeast Pityrosporum ovale, an organism believed to be involved in the pathogenesis of dandruff. OBJECTIVE: Our purpose was to evaluate the safety and effectiveness of ketoconazole 2% shampoo versus selenium sulfide 2.5% shampoo and placebo shampoo in patients with moderate to severe dandruff. METHODS: Features assessed included adherent and loose dandruff scores, presence or absence of irritation, itching, yeast cells, and global improvement rating by the investigator. RESULTS: A total of 246 patients were included. Mean total adherent dandruff score declined throughout the treatment period with both ketoconazole 2% and selenium sulfide 2.5% shampoos significantly better than placebo at all visits. Ketoconazole was statistically superior to selenium sulfide at day 8 only (p = 0.0026). Both medicated shampoos were significantly better than placebo for reducing irritation and itching. Of the nine adverse experiences reported during the treatment phase, all involved patients treated with selenium sulfide 2.5% shampoo. CONCLUSION: Both ketoconazole 2% shampoo and selenium sulfide 2.5% shampoo are effective in the treatment of moderate to severe dandruff; however, ketoconazole 2% shampoo appears to be better tolerated.

Adolescent↗
PubMed1990

Comparative embryotoxicity of selenite and selenate: uptake in murine embryonal and fetal tissues and effects on blastocysts and embryonic cells in vitro.

The placental transfer and distribution pattern of selenium (Se) in embryonic and fetal tissues after intravenous injection of Na2(75)SeO3 (Se4+) or Na2(75)SeO4 (Se6+) has been investigated in mice in early, mid, and late pregnancy by use of whole-body autoradiography combined with gamma-counting. The given doses correspond to 45 micrograms Se/kg. In order to compare the direct toxicity in early embryonic stages, the two valence forms were studied by using in vitro systems with (1) mouse blastocysts and (2) chick embryo fibroblasts, differentiating into chondrocytes. The embryonic and fetal uptake after administration of Se4+ and Se6+ was almost identical. The placental transfer of Se was restricted but, nevertheless, increased with time after dosing and with progression from embryonic through fetal stages thereby suggesting active placental transfer. The highest uptake in the embryo was observed in the neuro-epithelium while the eye, liver and skeleton dominated the distribution pattern in the fetal period. Selenite (Se4+) was more toxic than selenate (Se6+) in the in vitro system, in which embryonic mesenchymal limb bud cells differentiated into chondrocytes, as well as in the blastocyst culture system. The results may suggest a direct effect of Se in the embryo as explanation to reported malformations in experimental studies.

Animals↗
PubMed1990

Studies on selenate and selenite absorption by sheep ileum using an everted sac method and an isolated, vascularly perfused system.

1. Using everted sacs of sheep ileum, selenate uptake was shown to be more rapid than selenite uptake. 2. Sulphate, thiosulphate and ouabain all inhibited the uptake of selenate. A Na+K(+)-ATPase is probably responsible for energizing the ileal brush-border transport of selenate. 3. The isolated, vascularly perfused ileum was shown to absorb selenate more rapidly than selenite. 4. The perfusion system described would appear to be a useful tool for studying the kinetics of intestinal absorption and the measurement of metabolic transformations within the mucosa.

Animals↗
PubMed1985

Selenocystine is not a cystine antimetabolite in L1210 cells.

Selenocystine inhibited the growth in culture of murine L1210 leukemia cells to a greater extent when the cells were supplemented with a high concentration of cystine for optimal growth. Cells which grew suboptimally in a limiting cystine concentration were inhibited to a lesser extent. In this case, the time of onset of selenocystine inhibition coincided with the time of termination of growth at the lower cystine concentration. These observations are contrary to expectation for action of an antimetabolite, and it is concluded that selenocystine cannot be considered a cystine antagonist.

Animals↗
PubMed1981

In vivo incorporation of selenalysine in Escherichia coli proteins and its effects on cell growth.

The presence of selenalysine in the culture medium at concentration ranging from 0.05 to 0.3 mM inhibits Escherichia coli growth rate and cell viability. The inhibition of cell growth rate can be imputed to the inhibition of protein synthesis and can be only partially reverted by lysine. Selenalysine is incorporated into cellular proteins in substitution of and in competition with lysine, reaching the value of about 1% as molar fraction with respect to the total amino acids, and substituting up to 14% of protein lysine. The effect of selenalysine on cell viability can be correlated to the extent of its incorporation into proteins, and can be completely reverted by lysine. However, substitution up to 5% of protein lysine by selenalysine does not affect the viability, thus indicating that some degree of substitution can be well tolerated by the cell.

Bacterial Proteins↗
PubMed1989

Cloning of a new bidirectionally selectable marker for Aspergillus strains.

Mutants that lack adenosine triphosphate sulfurylase (ATPsase; EC 2.7.7.4) are unable to use sulfate as sole source of sulfur and are also resistant to selenate. These mutants, denoted sC-, are readily obtained from any strain of Aspergillus niger or Aspergillus nidulans by the strong selection for selenate resistance. We have cloned the gene encoding ATPsase from A. nidulans by complementation of an sC mutant strain of A. nidulans with a gene library and show that plasmids containing this gene transform both A. niger and A. nidulans sC- strains, restoring their ability to grow on sulfate as sole sulfur source. The fact that strong selection for either sC+ or sC- can be applied provides a simple way of delivering genetically engineered constructs to any strain of A. niger including strains of industrial importance. In addition, this system is useful for gene replacements and other genomic DNA manipulations in Aspergillus species.

Aspergillus nidulans↗
PubMed1985

Effects of sodium selenite and selenate on DNA and RNA synthesis in vitro.

The effects of sodium selenite and sodium selenate on DNA and RNA synthesis have been examined using intact HeLa cells, isolated nuclei and extracted polymerases. Selenate had no effect on any of the systems examined. Selenite inhibited DNA synthesis in intact cells and in isolated nuclei, and to a limited extent also inhibited DNA polymerase alpha. Selenite also inhibited RNA synthesis in intact cells and alpha-amanitin resistant RNA synthesis in isolated nuclei (i.e., synthesis catalyzed by RNA polymerase I and III). It had no effect on alpha-amanitin sensitive synthesis (catalyzed by RNA polymerase II) at concentrations up to 500 microM. However, transcription of exogenous DNA by extracted RNA polymerase II (as well as by polymerase I and III) was inhibited by selenite.

Catalysis↗
PubMed1987

The effects of selenium on the distribution of mercury in the organs of the black bullhead (Ictalurus melas).

Following i.p. mercuric chloride injections, the mercury was deposited primarily in the kidneys. Simultaneous selenium injections prevented mercury induced osmoregulatory failure even though selenium strongly promoted the movement of mercury to the kidneys and its deposition in an approximate 1:1 mercuric selenite ratio. Whole-body retention of mercury was not altered by simultaneous subcutaneous injections of sodium selenite.

Animals↗
PubMed1990

Embryotoxicity and dose-response relationships of selenium in hamsters.

Pregnant hamsters were treated with selenite, selenate, and selenomethionine during the critical stages of embryogenesis. The dosing regimens were oral, intravenous, and osmotic minipump infusion. Malformations, mainly encephaloceles, were noted with oral and intravenous selenite and selenate but were associated with maternal toxicity manifested by inanition and weight loss. Fetal body weights and lengths were reduced in a dose-dependent manner with the inorganic forms. Single oral doses of selenomethionine above 77 mumol/kg induced similar malformations but not when the dose was delivered orally over four days nor by minipump over several days. Fetal body weights and lengths were decreased by selenomethionine in a dose-dependent manner. Maternal toxicity was pronounced with the higher doses of selenomethionine. Assigning a specific teratogenic effect to selenium is confounded by maternal toxicity.

Abnormalities, Drug-Induced↗