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Biomedical subjects

E Walum

Publications and source records attributed to E Walum.

At least 37 records · Page 2Linked to original sources
PubMed1992

The effect of six sesquiterpenoid unsaturated dialdehydes on cell membrane permeability in human neuroblastoma SH-SY5Y cells.

The effect of six sesquiterpenes containing an unsaturated dialdehyde functionality, on cell membrane permeability in the human neuroblastoma cell line SH-SY5Y has been studied. The kinetics of the membrane leakage after addition of the sesquiterpenes were determined by measuring the efflux of radioactivity from cells preloaded with tritiated 2-deoxyglucose. The concentrations that gave 5% and 20% efflux of radioactivity as compared with control cells (EC5 and EC20) were determined for each compound. In spite of the structural similarities between the compounds, the effects on cell membrane permeability varied considerably. EC20 for polygodial, which is the most active compound, is 2.5 microM after 20-min incubation, but no leakage could be determined for merulidial even at concentrations as high as 4 mM. Rather, this compound seems to stabilize or fix the cell membrane and a lower efflux of radioactivity was observed as compared to the control cells. A quantitative structure-activity relationship analysis for the five active compounds showed a good correlation between the membrane leakage activity and certain chemical characteristics. Structural features strongly correlated with high activity were found to be: The geometry and the atomic charges of the unsaturated dialdehyde functionality, the dipole moment, the energy difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital and the lipophilicity.

Aldehydes↗
PubMed1989

MEIC--a new international multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests.

A new international project to evaluate the relevance for human systemic and local toxicity of in vitro tests of general toxicity of chemicals has been organized by the Scandinavian Society of Cell Toxicology under the title Multicenter Evaluation of In Vitro Cytotoxicity (MEIC). The basic assumptions underlying the project, as well as the practical goals and the design of the program are outlined. The list of the first 50 reference chemicals is presented. The chemicals are an otherwise unbiased selection of compounds with known human acutely lethal dosage and blood concentrations, including LD50-values in the rat or mouse. Most agents also have other data on human toxicity and toxicokinetics, including more extensive animal toxicity data. International laboratories already using or developing in vitro tests of various partial aspects of general toxicity are invited to test the substances, the results of which will be evaluated by us. The predictivity of the in vitro results for both partial and gross human toxicity data will be determined with combined use of univariate regression analysis and soft multivariate modeling. The predictivity of the in vitro results will be compared with the predictivity of conventional animal tests for the same chemicals. Finally, batteries of tests with optimal prediction power for various types of human toxicity will be selected. The need for and possible uses of such batteries are discussed.

Animals↗
PubMed1989

A combined in ovo-in vitro system for studies of volatile compounds on brain development: differential effects of carbon tetrachloride on neurones and astrocytes.

A method for studies of organic solvent effects on the development of neurones and astrocytes is described. Chick embryos in ovo were exposed to a low concentration of carbon tetrachloride vapours. After the exposure, primary cultures of neurones and astrocytes were prepared from the brain hemispheres of the embryos. Toxic effects of the solvent were analyzed in the cultures during the course of cellular differentiation as changes in cell growth and morphology, respiratory activity, and biochemical properties characteristic of each cell type. The development of neurones from embryos exposed from day 5 to day 8 to 25 p.p.m. of carbon tetrachloride was not affected by the exposure. On the other hand, growth rate and respiratory activity of astrocytes from embryos exposed from day 11 to day 14 to 25 p.p.m. of CCl4 were affected by the exposure, whereas no morphological changes or changes in the cyclic AMP levels could be observed. Consequently, low concentrations of carbon tetrachloride seem to affect the development of astrocytes rather than that of neurones in our experimental system.

Animals↗
PubMed1986

Lipid peroxidation and activities of tyrosine aminotransferase and glutamine synthetase in hepatoma and glioma cells grown in bovine colostrum-supplemented medium.

The growth stimulating properties of bovine serum and colostrum were compared in rat hepatoma (HTC) and glioma (C6) cell cultures. A colostrum concentration of 2% was optimal for HTC cells, which then reached a terminal density 40% of that in serum-supplemented medium. The corresponding figures for C6 cells were 10 and 81%, respectively. After 4 d in culture, levels of lipid hydroperoxides were measured and compared. Highest levels of lipid hydroperoxides were found in HTC and C6 cells grown in unsupplemented medium. HTC and C6 cells grown in serum supplemented medium contained levels of 52 and 64%, respectively, of that in unsupplemented medium. The corresponding levels for cells grown in presence of colostrum were 40% for HTC and 44% for C6 cells. To obtain information on any functional alterations in the cells due to the presence of colostrum the induction of tyrosine aminotransferase (EC 2.6.1.5) and glutamine synthetase (EC 6.3.1.2) by dexamethasone was studied. Although colostrum seemed to increase the basal activities of the enzymes, no significant effects on the degree of induction could be detected.

Animals↗
PubMed1986

Oxidative metabolism in cultured astroglial cells from rat brain.

Growth, morphology, glutamine synthetase activity, cytochrome C oxidase activity and respiratory activity of rat brain cultures enriched in astrocytes were studied during four weeks in culture. Two different polarographic methods were used for measurement of respiratory activity: one newly developed perfusion method leaving the cellular monolayer morphologically intact and still attached to the culture dish, and one traditional stirring method involving the removal of cells from the culture vessel. Regardless of the method used, a stable respiratory activity was registrated throughout the four weeks of culturing. Also the cytochrome C oxidase activity remained unchanged. In perfusion all absolute values for respiration were found to be higher than those obtained with the stirring method. The use of the stirring technique resulted in a doubling of oxygen consumption upon succinate addition. No such effect was seen in perfusion. It can thus be concluded that the removal of cultured astrocytic cells from their substratum alters their respiratory activity and their response to added substrates.

Animals↗
PubMed1985

Use of a perfusion technique for measurements of respiratory activity in cultured cells.

A method for measuring respiratory activity in anchorage-dependent cultured cells has been developed. This method is based on a technique that permits the perfusion of standard plastic culture dishes with attached cells. Basal respiratory activities were studied in two continuous cell lines of neural origin, neuroblastoma C1300 clone 41A3 and glioma 138MG. As compared to traditional measurements on detached cells, a fourfold increase in value was obtained. Investigations on membrane permeability suggested that the observed difference could be attributed to alterations in cell membrane integrity. Pretreatment with dibutyryl cyclic AMP, known to induce a morphological and biochemical differentiation in C1300 and 138MG cells, caused in both cell lines an enhanced respiration.

Animals↗
PubMed1985

Effects of dissolved carbon monoxide on the respiratory activity of perfused neuronal and muscle cell cultures.

In order to address the question of whether small amounts of dissolved CO may inhibit cellular respiration, cultured mouse neuroblastoma cells and primary cultures of chick neurons, rat astrocytes and chick skeletal muscle and heart cells were exposed to CO containing buffer solutions in a closed perfusion system. Oxygen uptake was measured simultaneously with two polarographic oxygen electrodes as the difference in partial pressure of oxygen between the inlet and outlet of the perfusion chamber. After registration of the basal respiratory activity, perfusion solutions containing 5 ul 02/ml were bubbled with CO or N2 at a rate of 200 ml/min for 120 sec. By this procedure the partial pressure of 02 was decreased to reach a value of about 50% of the initial 02 content for both gases. Perfusion was then continued for 30 min at a rate of 0.5 ml/min. The respiratory activity of all the perfused cell cultures, except chick neurons, was found to be inhibited (13-29%) by perfusion solutions bubbled for 120 sec with CO as compared to N2 controls. Of the cells from the nervous system, astrocytes were more sensitive than neurons. Apparently, small amounts of dissolved CO can inhibit cellular respiration in the presence of a physiologically adequate amount of oxygen.

Animals↗
PubMed1984

Cytotoxicity of cyclophosphamide and acrylamide in glioma and neuroblastoma cell lines cocultured with liver cells.

A method for the cocultivation of nervous system cells with liver cells has been developed. When acrylamide was tested using the cocultivation procedure no significant liver metabolism-mediated changes in the cytotoxicity in C6 culture were detected. In neuroblastoma N1E115 cultures the toxicity was increased by induced chick hepatocytes at high acrylamide concentrations.

Acrylamide↗
PubMed1984

On the application of cultured neuroblastoma cells in chemical toxicity screening.

The acute toxic action of a number of common chemicals was tested by their ability to cause detachment of cultured mouse neuroblastoma C1300 cells. A TD25 value was obtained by graphic estimation of the concentration needed to cause 25% of the total cell number to detach. These TD25 values were compared with LD50 values obtained from the literature, and they were found to correlate with a coefficient of 0.86. For six of the tested substances-diuron, butylated hydroxytoluene, benzidine, cyclophosphamide, Na2SeO3, and KCN-a very poor correlation was obtained. These diverging results could be ascribed to deficiencies in the neuroblastoma cell detachment test and emphasize the necessity for combined in vitro test procedures.

Animals↗
PubMed1984

Adenosine analogues stimulate cyclic AMP-accumulation in cultured neuroblastoma and glioma cells.

The effect of three stable adenosine analogues, L-phenylisopropyl-adenosine (L-PIA), 2-chloroadenosine, and adenosine 5'-ethylcarboxamide (NECA), on cyclic AMP accumulation was studied in five different cell lines derived from the nervous system. In N18-neuroblastoma cells, with cholinergic properties, all three analogues caused an increased accumulation of cyclic AMP with the following relative order of potency: NECA greater than 2-chloroadenosine greater than L-PIA. The half maximal effect of NECA was obtained at close to 10(-8) M concentration. In the two other neuroblastoma cell lines, 41A3 with cholinergic and NIE115 with adrenergic properties, the two analogues NECA and PIA had similar effects. In glioma C6 and 138 MG cells NECA was also found to be more potent that PIA in elevating cyclic AMP levels. However, the absolute potency of NECA in these cell lines was almost 100 times lower. Phosphodiesterase (PDE) activity in crude homogenates of the five cell lines showed essentially similar Km and Vmax, with the exception that the three neuroblastoma cell lines showed biphasic, the glial cell lines monophasic Eadie-Hofstee plots. Theophylline was equally potent as an inhibitor of PDE in all cell lines, but the non-xanthine, inhibitor rolipram, was more potent against neuroblastoma than glial cell PDE. These results indicate that all five cell lines have adenosine receptors of the A2-subtype. However, the apparent affinity of the adenosine analogues to these receptors was markedly different between the neuroblastoma and glial cell lines. The absolute potency of adenosine analogues may be a poor criterion to classify adenosine receptors, into A1 and A2 subtypes, especially when intact cells are used.

2-Chloroadenosine↗
PubMed1983

Growth and morphology of neuronal cell lines cultured in perfusion.

To optimize culture conditions and gain a more reliable culturing system for studies of metabolic properties of neuronal cells, a simplified perfusion chamber was developed. It consists of two parts: a perfusion block and a standard plastic culture dish. To confirm the suitability of this chamber for continuous culturing of anchorage-dependent cells, the growth and morphology of the four neuronal cell lines, glioma C6 and glioma 138MG, neuroblastoma C1300, clones N1E115 and N18 were followed for 4 d using both traditional and perfusion techniques. A marked increase in growth and a decrease in the degree of morphological differentiation were obtained with the latter technique compared to the former.

Animals↗
PubMed1983

Effects of mercuric chloride on the membrane integrity of cultured cell lines.

The effects of mercuric chloride on the membrane integrity of neuronal (N1E115), glial (138MG), muscle (L6) and liver (BRL123) cells in culture were studied. Alterations in passive membrane permeability were investigated in a perfusion system by following the efflux of radioactivity from cells preloaded with tritiated 2-deoxy-D-glucose. The efflux increased rapidly in the presence of a low concentration of HgCl2 (10(-5) M). The cell lines exhibited differential sensitivity to HgCl2 in the following order: BRL greater than L6 greater than N1E115 greater than 138MG. This differential sensitivity was confirmed by the alterations in the structure of the cell surfaces as observed in the scanning electron microscope. It is suggested that 2-deoxy-D-[3H]glucose may be a suitable probe in studies of membrane lesions caused by toxic substances.

Animals↗
PubMed1983

Acute toxicity testing in cultures of mouse neuroblastoma cells.

Cultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterparts in vivo. In order to test the possibility of using C1300 cells as alternative to experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2,HgCl2 ppDDT, n-butanol, benzene, dioxan, n-propanol, aceton and t-butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50 values. In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25 values and LD50 values. Good correlations between in vitro and in vivo tests have also been reported by others. One possible explanation to these findings could be simplified in vivo toxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simple in vitro tests may be used for predicting acute toxicity of certain groups of substances.

Animals↗
PubMed1982

Membrane lesions in cultured mouse neuroblastoma cells exposed to metal compounds.

Tritiated 2-deoxy-D-glucose (dGlc) was rapidly taken up into cultured mouse neuroblastoma C1300 cells (clone 41A3). Upon perfusion the preloaded cultures slowly released radioactivity as [3H] 2-deoxy-D-glucose-6-phosphate ([3H]dGlc-6-P) (rate const. = 0.017 min-1) from a pool corresponding to 74% (t1/2 = 41 min) of the total radioactivity incorporated. Destruction of the plasma membrane of the cells by means of Triton X-100 (1.0%) resulted in a rapid and total release of the radioactivity. CH3HgCl, HgCl2, (C2H5)3SnCl and K2Cr2O7 all caused an increase in the passive cell membrane permeability to [3H]dGlc-6-P. A membrane toxic concentration (MTC) was defined as the concentration of the tested metal compound giving rise to an increase in the relative efflux from 1.0 to 1.2 during 60 min perfusion. Using this MTC-value, the membrane toxicity of the compounds could be ranked in the following order: CH3HgCl (MTC = 9 x 10(-7) M) greater than HgCl2 (MTC = 6 x 10(-6) M) greater than (C2H5)3SnCl (MTC = 3 x 10(-4) M) greater than K2Cr2O7 (MTC = 7 x 10(-4) M). Since this differential toxicity is in accordance with other reports it is concluded that 2-deoxy-D-glucose (dGlc) may be used together with 41A3 cells to screen metal compounds for their membrane toxicity.

Animals↗