Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When irradiated with broad-band visible light in the presence of merocyanine 540 (MC540), murine leukemia L1210 cells grown under selenium-deficient conditions (Se(-) cells) accumulated lipid hydroperoxides and lost viability more rapidly than selenium-satisfied (Se(+) cells). These findings suggest that cytoprotection against photoperoxidation and photokilling is mediated at least in part by selenoperoxidase (SePX) action. Similar protection against photoinactivation of an intrinsic membrane enzyme, the Na+,K(+)-ATPase, has been observed. Thus, irradiation of MC540-sensitized Se(-) cells resulted in an immediate and progressive inactivation of ouabain-sensitive Na+,K(+)-ATPase; by contrast, activity loss in Se(+) cells was preceded by a prominent lag. Enzyme photo-inactivation in Se(-) cells was inhibited by ebselen, an SePX mimetic, confirming that SePX(s) is (are) involved in natural protection. Desferrioxamine treatment (iron sequestration/inactivation) resulted in higher hydroperoxide levels and slower Na+,K(+)-ATPase inactivation during MC540/light exposure, whereas ferric-8-hydroxyquinoline treatment (iron supplementation) had the opposite effect. Thus, iron appears to play an important role in both of these processes. In contrast, photoinactivation of another intrinsic enzyme in L1210 cells, acetylcholinesterase (AChE), was unaffected by selenium or iron manipulation. On the basis of these findings, we propose that lipid peroxidation plays an important role in the photoinactivation of Na+,K(+)-ATPase, but not AChE. This is consistent with the fact that Na+,K(+)-ATPase's active site lies within the membrane bilayer, whereas AChE's active site lies outside the bilayer.
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PMID:Cytoprotection against merocyanine 540-sensitized photoinactivation of the Na+,K(+)-adenosine triphosphatase in leukemia cells: glutathione and selenoperoxidase involvement. 801 11

Enrichment of rat daily diets by 1-2 (up to 5) mg selenium increased nonspecific resistance of animals to ionizing radiation. Incidence of mammary, pituitary, and thyroid tumors as well as of leukemia were lower as compared with control animal group given no selenium.
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PMID:[Study of the anticarcinogenic characteristics of the trace element, selenium, sanitary-hygienic experiment]. 822 90

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.
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PMID:Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group. 828 53

Murine leukemia L1210 cells grown for 2-3 weeks in the presence of 1% serum without selenium supplementation [L.Se(-) cells] typically exhibited < 10% of the glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity of selenium-satisfied controls [L.Se(+) cells]. Concomitant with diminished GPX and PHGPX activity was a 1.5- to 2.0-fold increase in catalase (CAT) activity, which reverted to control levels when L.Se(-) cells were given sufficient Se for full expression of selenoperoxidase activity. Selenium manipulation affected total glutathione content similarly, but had no effect on glutathione-S-transferase or superoxide dismutase activity. Long-term growth under Se-deficient conditions resulted in a progressive additional increase in CAT activity, which maximized after ca. 5 months. These cells [referred to as L'.Se(-)] attained CAT activity levels at least 100-times greater than those of Se-supplemented [L'.Se(+)] controls, whereas their glutathione content remained elevated by approximately 70%. Supplying L'.Se(-) cells with Se resulted in a rapid elevation to full GPX activity; however, CAT failed to decline in this case, suggesting that a selection for stable CAT hyperexpressing variants had been accomplished. Quantitative immunoblot analysis indicated that the high CAT activity of L'.Se(-) cells is accounted for by an elevated level of enzyme protein. Induction of CAT and selection for CAT-rich phenotypes, as apparent for Se-starved L1210 cells, was not observed in human K562 counterparts, which lack GPX and express only a low level of PHGPX. L.Se(-) cells were found to be more sensitive to H2O2-induced killing than L.Se(+) controls, whereas L'.Se(-) cells were exceedingly more resistant to H2O2 than L'.Se(+) counterparts. By contrast, L.Se(-) and L'.Se(-) cells were both more sensitive to t-butyl hydroperoxide than Se(+) controls, consistent with CAT being unimportant in the detoxification of this peroxide compared with GPX. This appears to be the first reported evidence for CAT hyperexpression in response to selenium deprivation.
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PMID:Hyperexpression of catalase in selenium-deprived murine L1210 cells. 834 49

Merocyanine 540 (MC540) is a lipophilic photosensitizing dye of biomedical interest in connection with its ability to preferentially inactivate leukemia cells in bone marrow grafts and enveloped viruses in blood products. Evidence that iron plays a role in dye-mediated photokilling is presented in this report. When sensitized with MC540 and irradiated with visible light, cultured murine leukemia L1210 cells underwent lipid peroxidation (accumulation of iodometrically detectable lipid hydroperoxides) and photokilling (loss of clonogenic capacity). Selenium-deficient [Se(-)] cells, which expressed minimal selenoperoxidase activity, were found to be more sensitive to photoperoxidation and photokilling than selenium-replete [Se(+)] controls. Since redox active iron in the presence of electron donors has been shown to exacerbate photoperoxidative damage in isolated membrane systems, it was of interest to examine the possible role of iron in MC540/light-induced cytotoxicity. Involvement of iron was established by showing (i) that desferrioxamine (a high-affinity chelator and redox inhibitor of Fe3+) acted protectively on Se(-) and Se(+) cells and (ii) that treating these cells with sublethal concentrations of the lipophilic chelate ferric 8-hydroxyquinoline [Fe(HQ)2] made them much more sensitive to photokiling and thiobarbituric acid-detectable lipid peroxidation. Lehal damage induced by t-butyl hydroperoxide was also amplified by Fe(HQ)2. Fe(HQ)2-enhanced photoperoxidation and photokilling were suppressed by alpha-tocopherol, suggesting that iron-catalyzed free radical reactions were involved. A mechanism based on iron-mediated one-electron reduction of nascent photoperoxides is proposed. We believe that under the conditions used, toxic one-electron chemistry overwhelms two-electron detoxification catalyzed by GSH-dependent selenoperoxidase(s).
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PMID:Photodynamic action of merocyanine 540 on leukemia cells: iron-stimulated lipid peroxidation and cell killing. 843 51

The variation of the selenium status of leukocytes was used as a tool to investigate the influence of selenium-containing glutathione peroxidases on the formation of 5-lipoxygenase metabolites in vitro and ex vivo. Selenium-deficient rat basophilic leukemia cells had < 1% of control glutathione peroxidase activity and 35% of control phospholipid hydroperoxide-glutathione peroxidase activity. Upon stimulation, these cells released an 8-fold amount of lipoxygenase metabolites compared to controls. No (5S)-hydroperoxyeicosatetraenoic acid was detectable in whole cells; however, it was found in homogenates of selenium-deficient cells. Addition of 0.25 microgram/ml selenium to selenium-deficient cells restored control phospholipid hydroperoxide-glutathione peroxidase activity within 8 h, whereas glutathione peroxidase activity needed 7 days. 12 h after resupplementation, selenium-deficient cells had 3% glutathione peroxidase and 100% phospholipid hydroperoxide-glutathione peroxidase activity compared to controls. Resupplemented cells released control amounts of 5-lipoxygenase metabolites, indicating that restoration of phospholipid hydroperoxide-glutathione peroxidase activity is associated with a selenium-adequate leukotriene metabolism. Leukocytes that were isolated from selenium-deficient rats released a 7-fold amount of total lipoxygenase metabolites compared to cells from control animals. By injecting normally fed rats with 500 micrograms/kg selenium as Na2SeO3, leukocyte phospholipid hydroperoxide-glutathione peroxidase activity was raised 8-fold within 114 h compared to controls. Leukocytes from these animals produced significantly less lipoxygenase metabolites than controls. These findings indicate that phospholipid hydroperoxide-glutathione peroxidase activity is primarily responsible for the reduction of 5-hydroperoxyeicosate-traenoic acid and therefore governs the actual activity of leukocyte 5-lipoxygenase via regulating the tone of endogenous hydroperoxides.
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PMID:Selenoenzymes regulate the activity of leukocyte 5-lipoxygenase via the peroxide tone. 845 1

Murine leukemia L1210 cells grown for 5-7 d in the presence of 1% serum without added selenium [Se(-) cells] expressed < 5% of the glutathione peroxidase (GPX) activity of selenium-supplemented controls [Se(+) cells]. Clonogenic survival assays indicated that t-butyl hydroperoxide (t-BuOOH) is much more toxic to Se(-) cells (LC50 approximately 10 microM) than to Se(+) or selenium-repleted [Se(-/+)] cells (LC50 approximately 250 microM). Hypersensitivity of Se(-) cells to t-BuOOH was partially reversed by treating them with Ebselen, a selenoperoxidase mimetic; thus, selenoperoxidase insufficiency was probably the most serious defect of Se deprivation. Cytotoxicity of t-BuOOH was inhibited by desferrioxamine and by alpha-tocopherol, indicating that redox iron and free radical intermediates are involved. Elevated sensitivity of Se(-) cells to t-BuOOH was accompanied by an increased susceptibility to free radical lipid peroxidation, which became even more pronounced in cells that had been grown in arachidonate (20:4, n-6) supplemented media. That glutathione (GSH) is required for cytoprotection was established by showing that Se(+) cells are less resistant to t-BuOOH after exposure to buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. Coupled enzymatic assays indicated that Se(+) or Se(-/+) cells metabolize t-BuOOH 20-25 times more rapidly than Se(-), consistent with the measured difference in GPX activities of these cells. Correspondingly, when challenged with t-BuOOH, Se(+) cells showed an initial loss of GSH and elevation of GSSG that exceeded that of Se(-) cells. It was further shown that like Se(-) cells, BSO- or BCNU-treated Se(+) cells metabolize t-BuOOH more slowly than nontreated controls. These results clearly indicate that selenoperoxidase action in the glutathione cycle is a vital element in cellular defense against toxic hydroperoxides.
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PMID:Selenoperoxidase-mediated cytoprotection against the damaging effects of tert-butyl hydroperoxide on leukemia cells. 845 83

The evaluation of the influence of different environmental carcinogenic factors requires interdisciplinary cooperation. Related studies include epidemiological surveys and air, water and soil, chemical, toxicological, and microbiological analyses, supplemented by experimental verification of suspected ecological pathogens and cofactors. A balance of carcinogens and protective agents in the external environment and in the human body is recommended for an ecologically oriented prevention. Toxicological control of the food chain using modern technology (Proton-induced X-ray emission (PIXE), nuclear activation analysis, and induced coupled plasma) should be integrated with microanalyses at the cellular level (by X-ray scanning electron microscopy, nuclear magnetic response, PIXE, and spontaneous and delayed chemiluminescence for balance of free-radicals and their scavengers). A pilot cross-disciplinary study conducted in the area of a "cluster" of human neoplasms and cattle leukemia, in comparison with control villages in Poland, showed an excess in Pb, Hg, Ni, Rb, K, Mn, Cr, and Zn, accompanied by a nutritional deficiency in Mg, Ca, Fe, Co, and Se in the food chain of the "cluster." The living and breeding houses in this area were significantly more contaminated with the toxicogenic molds Aspergillus flavus and Penicillium meleagrinum and by nitrate and nitrite in the drinking water. Our experiments showed that selenium deficiency stimulated the growth of fungi and some bacteria and increased the immunosuppressive and teratogenic effects of aflatoxin B1. New methods of protection of the indoor environment against microbiological contamination and laser-related biotechnology for nutritional prevention of selenium deficiency and associated risk of neoplasms have been introduced. Primary prevention requires a large scale application of highly sensitive methods for early detection of risk factors in the environment, food, water, and at the personal level, as well as education of the society and an integrated common corrective action.
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PMID:Environmental risk factors of cancer and their primary prevention. 845 68

Selenium is known to inhibit growth rate of neoplastic cells. We have investigated the role of selenium (Se) in resensitization of the adriamycin (ADR) resistant murine P388/ADR cells to the action of ADR. The experiments were performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se was observed to be dose dependent i.e. Se at a concentration of 5 x 10(-8)M resulted in potentiation of DNA biosynthesis whereas 5 x 10(-6)M and 5 x 10(-5)M Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR there was a further increase in inhibition of DNA biosynthesis. In P388/ADR cells, Se at 5 x 10(-6)M and 5 x 10(-8)M concentration resulted in inhibition of DNA biosynthesis, which increased further when combined with ADR indicating resensitization of these cells to the action of ADR. The inhibition was observed to be partially irreversible. These results were further confirmed in the in vivo and in vitro bioassays where the Se and Se+ ADR treatments resulted in increased lifespan of tumor bearing mice.
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PMID:Selenium (Se) cytotoxicity in drug sensitive and drug resistant murine tumour. 854 63

The selenium and TBARS concentrations and glutathione peroxidase activity were measured in the plasma of children with leukemia, lymphoma and histiocytosis X. A group of fifty-four children aged 1 to 16 years was divided into the following age groups: 1-3, 3-7, 7-16 years. In the patients aged 3-7 and 7-16 years, plasma selenium concentration and glutathione peroxidase activity were significantly lower than in age-matched healthy children.
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PMID:[Selenium, glutathione peroxidase and TBARS in plasma of children with malignant diseases of the hematopoietic system]. 868 59


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