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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth studies were done on a cultured rat liver cell line (RLC-GAI) grown in a chemically defined medium in the presence of lead nitrate. Lead reversibly inhibited the growth of these cells even after 6 d of exposure to the heavy metal. To compare lead sensitivity in various cell lines, GI50 and LD50 values were determined in the RLC-GAI cells as well as two glioma cell lines (B82 and C(6)) and a neuroblastoma cell line (N18). The LD50 values paralleled but were consistently lower than the GI50 values. Since lead is known to affect heme synthesis, hemin was added to test the possibilty of preventing the growth-inhibitory effect of the lead. The growth capacity of lead-treated cells did not change with the addition of hemin. It is thought that differentiated cultured cell lines such as these could be useful in examining the molecular mechanism of lead toxicity.
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PMID:Cellular and molecular toxicology of lead. I. Effect of lead on cultured cell proliferation. 56 52

The intracellular free calcium ion concentration ([Ca2+]i) of the neuroblastoma x glioma hybrid cell line, NG108-15, was measured using the 19F-nuclear magnetic resonance divalent cation indicator, 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA). The basal [Ca2+]i was measured to be 106 +/- 14 nM. Treatment with 5 microM lead (Pb) for 2 h produced a 2-fold increase in [Ca2+]i to 200 +/- 24 nM and a measurable intracellular free Pb2+ concentration ([Pb2+]i) of 30 +/- 10 pM. Intracellular free Zn2+ concentrations ([Zn2+]i) were also observed in the presence of Pb. This represents the first direct demonstration that Pb elevates the [Ca2+]i in neurons, thus providing evidence for a role of [Ca2+]i in mediating the neurotoxicity of Pb.
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PMID:Effect of lead on intracellular free calcium ion concentration in a presynaptic neuronal model: 19F-NMR study of NG108-15 cells. 260 23

Lead has been demonstrated to induce precocious glial differentiation both in vitro and in vivo. Lead-treated rat glioma (C6) and cerebellar astrocytes exhibited cytoplasmic extensions and the presence of glial endfeet after a 3-day exposure to 10(-6) to 10(-4) M PbCl2. In similar experiments no effect was noted in neuroblastoma (Neuro-2a) or on neurite outgrowth from chick spinal cord explants. This prodifferentiative effect on glia was also seen in the cerebella of postnatal rats in which the developmental expression of glial-specific glutamine synthetase activity was significantly increased up to postnatal day 12 after chronic exposure to lead from time of birth via their dam's drinking water (400 mg PbCl2/l).
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PMID:Chronic low level lead exposure precociously induces rat glial development in vitro and in vivo. 289 24

Lead exerts significant toxic effects on the nervous system, the hematopoietic system and the kidney. Specific cellular sites of action of this environmental pollutant have not been elucidated in the central nervous system. The present investigations were conducted to test the hypothesis that lead exposure perturbs glucocorticoid-mediated events in central nervous system hormonal target tissues. Utilizing the C6 glioma cell culture model in these studies, glucocorticoid receptor binding to its cytosolic receptor was investigated. Receptor binding studies yielded a Kd= 10.5 +/- 0.5 nM and a Bmax = 486 +/- 27 fmol/mg protein in untreated cells versus a Kd = 23.1 +/- 2.6 nM and Bmax = 472 +/- 35 fmol/mg protein in cells exposed to 10 microM lead acetate for 24 h. Presence of lead in these glial cells may decrease affinity of the glucocorticoid for its receptor without affecting receptor number. Treatment with 10 microM lead acetate for 48 h, resulted in a significant reduction in glucocorticoid-regulated glycerol phosphate dehydrogenase (GPDH) specific activity. These effects were not due to cell cytotoxicity assessed as cell number growth curves, [3H]thymidine incorporation or trypan blue exclusion. In protein kinase C (PKC) activity assays, treatment of cells with sodium or lead acetate and dexamethasone indicated that both lead and dexamethasone affect the distribution of PKC. In lead-treated cells cytosolic PKC activity was reduced 48% when compared to sodium acetate treated controls. Taken together, these results suggest that acute exposure of C6 cells to lead may inhibit processes involved in glucocorticoid-mediated signal transduction events within central nervous system hormonal target cells. Lead may perturb initial glucocorticoid binding events possibly by affecting PKC-mediated phosphorylations in the glucocorticoid signal transduction system.
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PMID:The acute effect of lead acetate on glucocorticoid receptor binding in C6 glioma cells. 902 May 12

A 72-year-man with previous lead poisoning presented with raised intracranial pressure and localizing neurologic signs. CT scans showed a high-grade glioma and extensive intracranial calcifications, which proved to be vascular in distribution on postmortem examination. The latter findings support the concept of dystrophic calcification following lead-induced cerebrovascular injury. Lead poisoning should be considered in the differential diagnosis of unexplained intracranial calcifications. There is also evidence from previous studies to suggest a causative relationship between lead poisoning and development of glioma.
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PMID:Intracranial vascular calcifications, glioblastoma multiforme, and lead poisoning. 909 Apr 26

Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured human glioma U-343MG cells were investigated considering uptake, toxicity and, in combination with radiation, clonogenic cells survival. The cells were exposed to 0-100 microM of the metals for a week before the evaluation. The tests showed a tendency to toxicity with 10 microM nickel although not significant (P > 0.05). Selenium, lead and mercury exerted a significant toxicity (P < 0.05) at 2.5 microM, 10 microM and 1 microM, respectively. To challenge the clonogenic cell survival capacity, the cells were irradiated with 60Co photons after being exposed to the highest nontoxic concentration of the different metals. The clonogenic cell survival tests, after irradiation, showed no significant change if the cells were exposed to 5 microM nickel, 0.5 microM selenium or 5 microM lead compared with those not exposed. Mercury, 0.1 microM, gave a relative reduction in survival compared with only irradiated cells of 58 +/- 17%. Thus, only mercury affected the radiation-induced damage and/or repair. When exposed to the highest nontoxic concentrations of the different metals, the cultures did not display a significant uptake ratio (metal concentration ratio of exposed cells to control cells) of nickel (3.1 +/- 3.3), only a small uptake ratio of selenium (4.0 +/- 0.4), while there was a large uptake ratio of both lead (2.6 +/- 1.7) x 10(2) and mercury (1.5 +/- 0.2) x 10(1). The results indicated that nickel was neither especially toxic nor influenced the clonogenic cell survival after irradiation. Mercury was more toxic and also influenced the radiation sensitivity. Lead was taken up strongly but did not influence the radiation sensitivity. Selenium accumulated but gave no detectable effect on the radiation sensitivity.
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PMID:Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured cells. Analysis of uptake, toxicity and influence on radiosensitivity. 935 73

Lead is an important neurobehavioral toxicant and may interfere with developmental processes in the brain resulting in impairment of its functions. U-373MG, a human glioma cell line, was cultured in Dulbecco's modified Eagles' medium supplemented with either 20 or 10% FBS (fetal bovine serum) to explore the possible indications for lead-induced toxicity. Although lead did not affect cell growth rate in concentrations ranging from 0.01 to 10 microM, it substantially altered gene expression analyzed by reverse-transcription polymerase chain reaction. With 10% FBS culture, lead affected the gene expression in a dose-dependent relationship. It enhanced the expression of tumor necrosis factor-alpha (TNF-alpha), but decreased those of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), gamma-aminobutyric acid (GABA) transaminase, and glutamine synthetase. With 20% FBS culture, lead also profoundly increased TNF-alpha and IL-1beta; however, it did not extensively affect the other genes examined above. Thus, the highly sensitive changes of gene expression of these cytokines or metabolic enzymes after treatments with lead acetate evidenced their usefulness as indicators for in vitro measurement of lead-induced neurotoxicity.
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PMID:In vitro aberrant gene expression as the indicator of lead-induced neurotoxicity in U-373MG cells. 1083 33

The induction of apoptotic cell death by cadmium was investigated in eight mammalian cell lines. Great differences in the cytotoxicity of cadmium were found with different cell lines: Rat C6 glioma cells turned out to be most sensitive with an IC50-value of 0.7 microM, while human A549 adenocarcinoma cells were relatively resistant with an IC50-value of 164 microM CdCl2. The mode of cadmium-induced cellular death was identified to involve apoptotic DNA fragmentation in three cell lines, i.e., in C6 glioma cells, E367 neuroblastoma cells and NIH3T3 fibroblasts. In C6 glioma cells, this process was investigated in detail. Internucleosomal DNA-fragmentation occurred 40 h after application of CdCl2 and was concentration-dependent between 1-100 microM CdCl2, followed by a decrease at higher concentrations due to necrotic processes. Apoptotic chromatin-condensation and nuclear fragmentation was observed 48 h after application of 2.5 microM CdCl2. Furthermore, cadmium (1 microM, 48 h) caused a breakdown of the mitochondrial membrane potential as shown by the decline in mitochondrial uptake of rhodamine 123. Also, we found an activation of caspase 9, a protease known to be activated in apoptotic processes following mitochondrial damage. Besides Cd2+, other toxic heavy metal ions (Hg2+, Pb2+, Ni2+, Fe2+, CrO4(2-), Cu2+ or Co2+) did not induce apoptotic DNA fragmentation in C6 cells. The only exception was Zn2+ which caused apotosis at high concentrations (>150 microM) whereas it protected against cadmium-induced apoptosis at low concentrations (10-50 microM).
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PMID:Cadmium-induced apoptosis in C6 glioma cells: mediation by caspase 9-activation. 1186 19

Lead (Pb) and mercury (Hg) are widespread environmental contaminants that induce prominent neural toxicity. Although the brain is not the major Pb and Hg depot in the body, these metals preferentially accumulate in astroglia to exert toxic effects. In this study, we examined the effects of Pb acetate and HgCl(2) on the expression of GRP78, a molecular chaperone in the endoplasmic reticulum (ER) that may provide cytoprotection in response to cellular stresses in the C6 rat glioma cell line. We also evaluated the DNA binding activities of several redox-regulated transcription factors in metal-treated cells. Our results showed that mRNA levels of GRP78 were up-regulated by Pb and Hg at 0.1 and 1 micro M, but down-regulated at higher concentrations (10 micro M). GRP78 protein levels increased in a concentration- and time-dependent manner in Pb and/or Hg-treated cells. Pb increased protein binding to the GST- Upsilon a antioxidant/electrophile response element (ARE/EpRE) and to the NF- kappaB consensus binding sequence of the cytomegalovirus 2 (CMB2) promoter, but decreased protein binding to the Ha-ras ARE/EpRE or to the c-fos 12-O-tetradecanoyl-phorbol-13-acetate (TPA) response element (TRE). In contrast, Hg activated DNA binding by all redox-regulated transcription factors. These studies shed some light on the molecular mechanisms of Pb and Hg toxicity in C6 rat glioma cells and suggest that GRP78 and oxidative stress may participate in the neurotoxic response to these metals.
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PMID:Induction of 78 kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells. 1511 Dec 46

Carboxylesterases, expressed at high levels in human liver and intestine, are thought to detoxify xenobiotics. The anticancer prodrug 7-ethyl-10-[4-1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is also metabolized by carboxylesterases to produce the active drug 7-ethyl-10-hydroxycamptothecin. Activation of CPT-11 by human intestinal carboxylesterase (hiCE) in the human intestine may contribute to delayed onset diarrhea, a dose-limiting side effect of this drug. The goal of this study was to develop small molecule inhibitors selective for hiCE to circumvent or treat the toxic side effects of CPT-11. A secondary goal was to develop molecules that specifically inhibit activation of CPT-11 by a rabbit liver carboxylesterase (rCE). rCE is the most efficient CPT-11-activating enzyme thus far identified, and this enzyme is being developed for viral-directed enzyme prodrug therapy applications. Based on in vitro assays with partially purified hiCE and rCE proteins and on growth inhibition assays using U373MG human glioma cells transfected to express hiCE or rCE (U373pIREShiCE or U373pIRESrCE), we identified specific inhibitors of each enzyme. Lead compounds are derivatives of nitrophenol having 4-(furan-2-carbonyl)-piperazine-1-carboxylic acid or 4-[(4-chlorophenyl)-phenylmethyl]-piperazine-1-carboxylic acid substitutions in the p position. Kinetic analysis of each compound for hiCE compared with rCE showed that the Ki values of the most selective of these inhibitors differed by 6- to 10-fold. In growth inhibition assays, nontoxic, low micromolar concentrations of these inhibitors increased the EC50 of CPT-11 for U373pIREShiCE or U373pIRESrCE cells by 13- to >1,500-fold. The four compounds characterized in this study will serve as lead compounds for a series of inhibitors to be constructed using a combinatorial approach.
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PMID:Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. 1529 73


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