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

The effects of catalase treatment were studied in two in vitro passaged ascites tumour lines (ATP C+ and EAT) and in three in vitro established human myeloid leukemia cell lines (HL-60; KG-1; KG-1a) characterized by the arrest of cells at different stages of maturation. The results demonstrate that catalase treatment favoured proliferation in the in vitro passaged ascites tumour cells, but not in the in vitro established leukemia lines. Enzyme assays on five in vitro cell lines revealed that catalase was only present in HL-60. Although glutathione peroxidase activity was initially found in all five cell lines, it disappeared from two ascites tumour cells when they were transferred in culture. It is hypothesized that catalase treatment favours ascites tumour cell proliferation because it replaces glutathione peroxidase in eliminating H2O2.
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PMID:Antioxidant enzymes and proliferative activity of cell lines of different origin. 261 35

Podophyllic acid piperidyl hydrazone nitroxide radical (GP-1) and etoposide (VP-16), derivatives of podophyllotoxin, inhibited DNA, RNA, protein and ATP synthesis of leukemia L7712 cells at a concentration of 5 micrograms/ml. Inhibitory extents were dependent on the exposure time from 3 to 24 h. The inhibitory rates of both drugs were about 15-66%. ID50 of GP-1 and VP-16 on the synthesis of L7712 cells at 24 h were 0.16 and 0.38 micrograms/ml, respectively. The dose-response curve of GP-1 was a parabolic one, while that of VP-16 was a straight line. The inhibition of GP-1 or VP-16 on DNA synthesis existed also after cells washing. It is suggested that the antitumor effects of GP-1 and VP-16 seem to be related to the damage of DNA template.
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PMID:[Podophyllic acid piperidyl hydrazone nitroxide radical and etoposide on nucleic acids and protein metabolism of leukemia L7712 cells in vitro]. 262 25

Protein kinase C (PKC) from human leukemia ML-1 cells was found to be susceptible to inhibition by the antineoplastic anthracycline adriamycin (ADR). Half-maximal inhibition (IC50 value) was observed at 200 microM. However, preincubation of ADR with phosphatidylserine (PS) or PKC enzyme, prior to the enzyme assay, reduced the IC50 value from 200 microM to 52 microM or 40 microM, respectively, indicating an affinity of ADR for PS, and also a possible action site for ADR on PKC molecules. Preincubation of ADR with diacylglycerol (DAG) before the PKC assay resulted in a more pronounced effect, i.e., a more rapid decline of PKC activity with an IC50 value of 7 microM. However, the IC50 for ADR inhibition was not altered when ATP, histone or Ca++ were preincubated with ADR. Studies of the kinetic nature of the inhibition revealed that ADR inhibition assumes competitive kinetics with respect to DAG. Therefore, the mechanism by which ADR inhibits PKC activity may involve a multi-site action: a primary interaction with DAG, and a secondary lower interaction with membrane PS and PKC apoenzyme.
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PMID:Adriamycin interacts with diacylglycerol to inhibit human leukemia protein kinase C. 270 49

Rapid kinetic techniques were used to study the transport and salvage of uridine and other nucleosides in mouse spleen cells. Spleen cells express two nucleoside transport systems: (1) the non-concentrative, symmetrical, Na+-independent transporter with broad substrate specificity, which has been found in all mammalian cells and is sensitive to inhibition by dipyridamole and nitrobenzylthioinosine; and (2) a Na+-dependent nucleoside transport, which is specific for uridine and purine nucleosides and resistant to inhibition by dipyridamole and nitrobenzylthioinosine. The kinetic properties of the two transporters were determined by measuring uridine influx in ATP-depleted cells and dipyridamole-treated cells, respectively. The Michaelis-Menten constants for Na+-independent and -dependent transport were about 40 and 200 microM, respectively, but the first-order rate constants were about the same for both transport systems. Nitrobenzylthioinosine-sensitivity of the facilitated nucleoside transporter correlated with the presence of about 10,000 high-affinity (Kd = 0.6 nM) nitrobenzylthioinosine-binding sites per cell. The turnover number of the nitrobenzylthioinosine-sensitive nucleoside transporter was comparable to that of mouse P388 leukemia cells. The activation energy of this transporter was 20 kcal/mol. Entry of uridine via either of the transport routes was rapidly followed by its phosphorylation and conversion to UTP. The Michaelis-Menten constant for the in situ phosphorylation of uridine was about 50 microM and the first-order rate constants for phosphorylation and transport were about the same. The spleen cells also efficiently salvaged adenosine, adenine, and hypoxanthine, but not thymidine.
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PMID:Na+-dependent and -independent transport of uridine and its phosphorylation in mouse spleen cells. 273 Sep 9

The arachidonate lipoxygenase from rat basophilic leukemia cells (RBL-1) is widely utilized as a model to dissect the primary enzymatic reactions leading to leukotriene formation. The purpose of the present study was to optimize the specific activity of 5-lipoxygenase prepared from a high speed supernatant of RBL-1 cell homogenates. Activation of 5-lipoxygenase was observed in the presence of micromolar levels of calcium. A synergistic enhancement of 5-lipoxygenase was observed upon addition of equally low levels of ATP; maximal activation was induced by 5 microM CaCl2 plus 5 microM ATP. Addition of a microsomal-membrane preparation and NADPH further augmented 5-HETE biosynthesis. High concentrations (330 microM) of NADPH reversed the microsomal-induced stimulation of RBL-1 5-lipoxygenase, resulting in enzyme inhibition.
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PMID:Optimization of cofactors which regulate RBL-1 arachidonate 5-lipoxygenase. 274 90

The novel tetrahydrofolate, 5,10-dideazatetrahydrofolic acid (DDATHF), was designed as an inhibitor of folate metabolism at a site other than dihydrofolate reductase. DDATHF has been shown to inhibit glycinamide ribonucleotide transformylase, a folate-requiring enzyme that catalyzes the first of two one-carbon transfer reactions in the de novo purine nucleotide biosynthetic pathway. Incubation of HL-60 promyelocytic leukemia cells with 5 x 10(-8) to 10(-5) M DDATHF resulted in a marked inhibition of growth after 48 h, with a complete cessation of cellular replication by day 4. Cell cycle analyses of DDATHF-treated HL-60 cells demonstrated an initial block in early S phase by day 3 followed by an accumulation of cells in the G1 and G2 + M phases of the cell cycle. Inhibition of growth was accompanied by a concentration-dependent increase in the percentage of mature myeloid cells that expressed nitroblue tetrazolium positivity, and a small increase in nonspecific esterase activity. Induction of differentiation and inhibition of growth by DDATHF were completely prevented by hypoxanthine and 5(4)-amino-4(5)-imidazole carboxamide, suggesting that depletion of intracellular purine nucleotide pools has an important role in the biological effects of this inhibitor. This possibility was confirmed by the finding that DDATHF caused a pronounced reduction in intracellular GTP and ATP levels within 2 h, with maximum decreases being observed by 24 h, a time interval which preceded the inhibition of cellular proliferation by this agent. Pyrimidine nucleoside triphosphate levels were markedly increased under these conditions. The findings indicate the importance of purine nucleotides to both the inhibition of growth and the induction of differentiation of HL-60 leukemia cells by DDATHF.
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PMID:Induction of HL-60 leukemia cell differentiation by the novel antifolate 5,10-dideazatetrahydrofolic acid. 275 15

By employing rat cardiac myocytes in culture and mouse L-1210 leukemia cells, we have compared different anthracycline analogs with respect to their ability to kill cardiac myocytes and tumor cells. Anthracyclines induced a decrease in cellular ATP and glutathione from both cardiac myocytes and L-1210 cells in a time- and concentration-dependent fashion. Moreover, the decrease in ATP in cardiac myocytes was followed by release of the cytoplasmic enzyme lactic acid dehydrogenase and of adenine nucleotides after anthracycline treatment. At very low concentrations of anthracyclines, at which ATP and glutathione were not affected, the drugs induced complete cessation of the growth of L-1210 cells. Some structural alterations in the anthracycline molecule resulted in parallel changes in antitumor activity and in cardiotoxicity. But other structural alterations resulted in dissimilar changes in antitumor activity and cardiotoxicity. Although the results indicate that the structural requirements for inducing cardiotoxicity and antitumor activity may be different, they also indicate that the mechanisms by which anthracycline causes cell death in tumor cells and cardiac myocytes may be the same.
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PMID:Structural requirements for anthracycline-induced cardiotoxicity and antitumor effects. 276 5

Changes in ATP levels of both Ehrlich ascites carcinoma and P388 leukemia cells were evaluated after 2 h of incubation in the presence of different concentrations of benfluron (BF), 7-dihydrobenfluron (DBF) and N-oxide of benfluron (NOBF). Up to the concentration of 37.5 mumol/l, none of the substances significantly depressed the ATP levels. A more expressive decrease in ATP levels was noted only at concentrations of 75 mumol/l and higher. BF proved the most effective, less effective was DBF, while NOBF was practically without any effect. Of the remaining cytostatic drugs, Mitoxantrone, CCNU and Me-CCNU, in particular, proved efficient in depressing ATP level. The latter becomes depressed already after 15 min of incubation in the presence of the highest concentrations of benfluron and 7-dihydrobenfluron.
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PMID:Effect of benfluron metabolites on ATP level in tumor cells. 277 Sep 28

2'-Deoxycoformycin (dCF), a potent adenosine deaminase inhibitor, has been reported to display greater toxicity for T than for B lymphoblasts. Since this compound can block DNA replication and since this effect is mediated by the intracellular ATP/dATP balance, its possible effect on DNA ligase was investigated. dCF at relatively low concentrations (1 microM), in association with dATP (100 microM), is a strong inhibitor of DNA ligase in T blasts, whereas it has no significant effect in B blasts at this concentration. The AMP-ligase complex is the target of the observed inhibition because the combined presence of the inhibitor and dATP results in a more stable dAMP-ligase complex. Because of this observation and of the greater adenosine deaminase activity observed in T cells, the dATP mediated dCF inhibition of ligase might be the crucial replication target of T cell toxicity. These observations are discussed in terms of T immunodeficiencies including Graft Versus Host Disease and related syndromes.
Leukemia 1989 Feb
PMID:dATP-mediated inhibition of DNA ligase by 2'-deoxycoformycin in T and B cell leukemia. 278 73

The mechanism of the depletion of ATP, recorded in the erythrocytes of adenosine deaminase-deficient children and of leukemia patients treated with deoxycoformycin, was investigated in normal human erythrocytes treated with this inhibitor of adenosine deaminase. Deoxyadenosine, which accumulates in both clinical conditions, provoked a dose-dependent accumulation of dATP, depletion of ATP, and increases in the production of inosine plus hypoxanthine. Concomitantly, there was an increase of AMP and IMP, but not of adenosine, indicating that catabolism proceeded by way of AMP deaminase. A series of nucleoside analogues (9-beta-D-arabinofuranosyladenine, N6-methyladenosine, 6-methylmercaptopurine ribonucleoside, tubercidin, ribavirin, and N-1-ribosyl-5-aminoimidazole-4-carboxamide riboside) also stimulated adenine nucleotide catabolism and increased AMP and IMP to various extents. The effects of deoxyadenosine and of the nucleoside analogues were prevented by 5'-iodotubercidin, an inhibitor of adenosine kinase. Strikingly, they were reversed if the inhibitor was added after the accumulation of nucleotide analogues and initiation of adenine nucleotide catabolism. Further analyses revealed linear relationships between the rate of phosphorylation of deoxyadenosine and nucleoside analogues and the increase in AMP and between the elevation of the latter above a threshold concentration of 10 microM and the rate of adenine nucleotide catabolism. Kinetic studies with purified erythrocytic AMP deaminase, at physiological concentrations of its effectors, showed that the enzyme is nearly inactive up to 10 microM AMP and increases in activity above this threshold. We conclude that the main mechanism whereby deoxyadenosine and nucleoside analogues stimulate catabolism of adenine nucleotides by way of AMP deaminase in erythrocytes is elevation of AMP, secondary to the phosphorylation of the nucleosides.
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PMID:Mechanism of adenosine triphosphate catabolism induced by deoxyadenosine and by nucleoside analogues in adenosine deaminase-inhibited human erythrocytes. 278 93


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