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)

Red cell reduced glutatione (GSH) and pyrimidine 5'-nucleotidase (Pry 5'-NT) were measured in a variety of myeloproliferative and lymphoproliferative disorders. Raised levels of GSH were found in chronic lymphocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, Waldenstrom's macroglobulinaemia and myeloma. Decreased activity of Pyr 5'-NT was found in acute myeloblastic leukaemia, acute lymphoblastic leukaemia, chronic granulocytic leukaemia, chronic lymphocytic leukaemia, Hodgkin's disease and non-Hodgkin's lymphoma. There was no correlation between the raised GSH levels and decrease Pry 5'-NT levels.
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PMID:Red cell pyrimidine 5'-nucleotidase and glutathione in myeloproliferative and lymphoproliferative disorders. 624 15

Rat basophilic leukemia cells have frequently been employed for investigating the pathways of leukotriene biosynthesis, a class of biologically active arachidonic acid metabolites. However, information is lacking on the levels of selenium-dependent glutathione peroxidase (Se-GSH-Px), non-Se-GSH-Px and glutathione S-transferases (GSH-S-Trs), key enzymes involved in fatty acid hydroperoxide metabolism and leukotriene biosynthesis in these cells. Both GSH-S-Trs and non-Se-GSH-Px reactions are catalyzed by the same enzyme. In the present studies, we have measured the enzyme activities of GSH-Px(s) and GSH-S-Trs in the 105,000 X g supernatant fraction of sonified RBL-1 cells. The specific activities for GSH-Px(s) toward H2O2, cumene hydroperoxide, and 15S-hydroperoxy-eicosatetraenoic acid (15S-HPETE) are 12.6, 17.9 and 26.9 nmoles X min-1 X mg-1 protein, respectively. A specific activity of 18.9 nmoles X min-1 X mg-1 protein with 1-chloro-2,4-dinitrobenzene was estimated for the GSH-S-Trs. Therefore, the cell fraction that exhibits 5-lipoxygenase activity also contains selenium and non-selenium glutathione peroxidases.
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PMID:Measurement of glutathione requiring enzymes involved in arachidonic acid cascade of rat basophilic leukemia cells. 644 77

The cytostatic unsaturated ketonucleosides, 1, 2, 3 and 4 are highly reactive sulfhydryl blocking agents. Kinetics of their reactions with reduced glutathione (GSH) were measured and their reactivity was compared to that of N-ethylmaleimide (NEM), acrylonitrile and chloroacetamide. Their reaction products with N-acetyl-L-cysteine (AcCys) were prepared and characterized by chemical analysis and nuclear magnetic resonance (NMR) spectroscopy. Compounds 1, 2 and 3 gave Michael type 1:1 addition products. Compound 4 reacted with AcCys by a three step mechanism; the primary addition product 8 underwent an unusual elimination reaction giving the unsaturated compound 9, which yielded the addition product 10 with AcCys. In the reaction with GSH, compound 4 behaved like a bifunctional SH alkylating agent. Compounds 1, 2, 3 and 4 also reacted with protein thiols as shown by their ability to inhibit lactate dehydrogenase (LDH). Unsaturated ketonucleosides had diversified effect on L1210 leukemia cells. While the most potent cytostatics, compounds 1 and 3, reduced considerably the membrane surface SH level, they were without effect on soluble intracellular protein thiols. In contrast, nucleosides 2 and 4, less active than the former, only slightly affected the membrane surface sulfhydryls and considerably depleted the intracellular soluble protein thiols. Only slight differences were found between the reactions of the four nucleosides with non-protein SH (NPSH). The correlation found between in vivo biological activity and cell membrane impairment suggests that selective alkylation of certain key membrane thiols by unsaturated ketonucleosides might be an important event in their biological effect.
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PMID:Interactions of cytostatic unsaturated ketonucleosides with sulfhydryl containing cell constituents. 661 5

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.
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PMID:Protective effect of reduced glutathione against cis-dichlorodiammine platinum (II)-induced nephrotoxicity and lethal toxicity. 668 12

Oral exposure of DBA/2 mice to benzo[a]pyrene (BP) has been shown to result in hematotoxicity which is manifested as aplastic anemia and leukemia. Since normal hematopoiesis is regulated by bone marrow stromal cells, in this study we have characterized the bone marrow stromal toxicity induced by BP and BP-derived metabolites, particularly quinones. Incubation of stromal cells with various concentrations of BP-1,6-, 3,6-, 6,12-, or 7,8-quinone for 24 hr resulted in a significant decrease of cell survival in a concentration-dependent manner, while cells treated with BP or BP-7,8-dihydrodiol did not exhibit any significant loss of cell survival. Among the BP quinones examined, BP-1,6-quinone was the most cytotoxic to stromal cells. The cytotoxicity induced by BP-1,6-quinone also exhibited a time-dependent relationship. Pretreatment of stromal cells with 1,2-dithiole-3-thione (D3T) resulted in a significant induction of both cellular reduced glutathione (GSH) content and quinone reductase (QR) activity in a concentration-dependent manner. However, D3T pretreatment did not offer any protection against BP-1,6-quinone-induced toxicity. Furthermore, dicumarol, a potent inhibitor of QR, or buthionine sulfoximine, a specific inhibitor of GSH biosynthesis, did not potentiate BP-1,6-quinone-induced cytotoxicity was not altered. However, incubation of stromal cells with BP-1,6-quinone resulted in a significant depletion of cellular ATP content and mitochondrial morphological changes, which preceded the loss of cell survival. In addition to BP-1,6-quinone, other cytotoxic BP quinones also exhibited a capacity to deplete cellular ATP level in stromal cells, while BP, which was not cytotoxic to stromal cells, did not elicit any significant decrease in cellular ATP level. These observations suggest that mitochondria may be a potential target of BP quinones. Overall, the above results indicate that neither cellular GSH and QR nor reactive oxygen species appear to be involved in BP quinone-induced stromal cell injury and that BP quinones may elicit cytotoxicity to stromal cells through directly disrupting mitochondrial energy metabolism.
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PMID:Characterization of benzo[a]pyrene quinone-induced toxicity to primary cultured bone marrow stromal cells from DBA/2 mice: potential role of mitochondrial dysfunction. 753 Aug 64

Benzene is a human carcinogen; exposure to benzene can result in aplastic anemia and leukemia. Data from animal models are frequently used in the risk assessment for benzene. In rodent studies, mice have been shown to be more sensitive to benzene-induced hematotoxicity than rats. In this regard, we have observed that bone marrow stromal cells from mice were significantly more susceptible to the cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) than cells from rats. Since cellular glutathione (GSH) and quinone reductase (QR) are known to play critical roles in modulating HQ-induced cytotoxicity, we have measured the GSH content and the QR and glutathione S-transferase (GST) activity in stromal cells from both species. In rat cells, the GSH content and the QR specific activity were 2 and 28 times as much as those from mice, respectively. GSH and QR in both mouse and rat stromal cells were inducible by 1,2-dithiole-3-thione (D3T). D3T pretreatment of both mouse and rat stromal cells resulted in a marked protection against HQ-induced toxicity. Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also provided a dramatic protection against HQ-induced toxicity. Conversely, dicoumarol, an inhibitor of QR, enhanced the HQ-induced toxicity in stromal cells from both mice and rats, indicating an important role for QR in modulating HQ-induced stromal toxicity in both species. Buthionine sulfoximine (BSO), which depleted GSH significantly in both species, potentiated the HQ-induced toxicity in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells with BSO resulted in a significant induction of QR, especially in rats. The failure of BSO to potentiate HQ-induced toxicity in rat stromal cells may be due to the concomitant induction of QR by BSO. Overall, this study demonstrates that the differences in stromal cellular GSH content and QR activity between mice and rats contribute to their respective susceptibility to HQ-induced cytotoxicity in vitro, and may be involved in the greater in vivo sensitivity of mice to benzene-induced hematotoxicity.
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PMID:Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: implications for benzene-induced hematotoxicity. 756 17

The expression of the ectoenzyme gamma-glutamyl transpeptidase (EC2.3.2.2., gamma GT) was investigated by flow cytometry on populations of peripheral blood mononuclear cells (PBMC) from healthy subjects and patients suffering from several types of leukemia before and under chemotherapy. In unstimulated PBMC, 28% of these cells were found to be gamma GT positive. The highest expression was measured on monocytes (CD14/gamma GT+ cells: 60%). Within the subsets of T lymphocytes (CD3/gamma GT+ cells: 18%) we saw no clear differences between CD4+ and CD8+ cells. B lymphocytes, NK cells, and activated cells showed low expressions (up to 10%). Treatment of PBMC with mitogens, alpha-IFN, IL-2, and GM-CSF did not affect the enzyme expression on normal mononuclear cells (MNC). However, a rapid increase of gamma GT+ cells was found in the presence of glutathione (GSH) and n-acetyl cysteine (nAC), particularly on monocytes, B cells, and NK cells. Comparing 40 healthy subjects and untreated patients suffering from leukemias, a significantly higher expression of gamma GT+ cells in the total MNC populations (B-CLL: 57%, CML: 62% gamma GT+ cells) was observed in B-chronic lymphocytic leukemia (B-CLL) and chronic myelogenous leukemia (CML), whereas other leukemias did not show clear differences. Most interestingly, the gamma GT expression was diminished in all populations of CML cells after 5 h of incubation in the presence of 10 units/ml IFN-alpha. These data suggest a possible protective role of gamma GT in MNC and a regulatory function of this enzyme in the development of CML.
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PMID:gamma-Glutamyl transpeptidase-cellular expression in populations of normal human mononuclear cells and patients suffering from leukemias. 759 85

The ectoenzyme gamma glutamyltransferase (GGT) a second messenger generating enzyme activity on the cytoplasmic membrane was biochemically analyzed in leukemic cells from patients with acute lymphoblastic and myeloid leukemias. The lower mean activity--0.594 IU/mg protein was noticed in patients with acute lymphoblastic leukemias (ALL), while the higher--0.956 IU/mg protein was found in acute myeloid leukemia patients (AML) in serum and 0.151 IU/mg protein in polymorphonuclear cells. The levels of the activity of glutathione reductase (GR) were increased but the activities of glutathione peroxidase (GSH Px) were significantly decreased in serum of leukemia patients.
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PMID:Activities of enzyme transducing extracellular signals--gamma glutamyltransferase and enzymes metabolizing glutathione in acute lymphoblastic and myeloid human leukemias. 761 77

The in vitro testing of antitumor drugs involves the use of mouse and human tumor cells. In particular, there is interest in developing agents active against human solid tumors. We examined several biochemical parameters that may contribute to the differential sensitivity of the cell lines used in our laboratory to the toxic effects of antitumor compounds. The tumor cell lines examined were of mouse (colon 38, L1210 leukemia, and C1498 leukemia) and human origin (CEM leukemia, CX1 colon, H116 colon, HCT8 colon and H125 lung). Quinone reductase activity was markedly different between leukemia and solid-tumor cell lines of either mouse or human origin, with increased activity being observed in the solid-tumor cell lines relative to the leukemia lines. GSH transferase activity also was generally increased in solid-tumor relative to leukemia cell lines. Superoxide dismutase activity and thiol levels were similar in leukemia and solid-tumor cell lines, except that thiol levels were very low in colon 38. Mouse cell lines from in vitro passage had somewhat higher activity of superoxide dismutase and thiol levels than did cells maintained in vivo, indicating relatively increased antioxidant defenses. The toxicity of 2,3-dimethoxy-1,4-naphthoquinone, a model quinone that exerts its toxic effects via production of reactive oxygen species, was significantly lower in mouse lines maintained in vitro than in those tested in vivo, whereas the toxicity of another quinone, menadione, was just slightly lower. Quinone reductase activity, GSH transferase activity, and thiol levels were significantly higher in the human lines than in the mouse lines. Accordingly, the toxicity of both quinones tended to be lower in the human lines than in the mouse lines.
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PMID:Detoxification ability and toxicity of quinones in mouse and human tumor cell lines used for anticancer drug screening. 772 Jan 71

P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6-Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment.
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PMID:Patterns of drug resistance parameters in adult leukemia. 777 47


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