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)

20 cats in a cat home were treated prophylactically and therapeutically with Baypamun HK. The animals were allocated into three groups as described. 7 freshly admitted clinically healthy cats were treated prophylactically on day 1, 2 and 9 with 1 ml Baypamun HK (group I). 7 cats, who already were allocated for one year in the home and were sick of the feline respiratory disease complex were treated as described for group I (group II). 6 further cats, who also showed symptoms of the feline respiratory disease complex and had stayed for one year in the home were treated with physiol.saline solution according to group I (group III). From all cats blood samples were taken at day 1, 3, 10 and 17. The blood samples were checked for antibodies against feline calicivirus (FCV), feline herpesvirus (FHV), panleukopenia virus (PLV), feline peritonitis virus (FIPV) and feline immunodeficiency virus (FIV). Also the occurrence of the feline leukemia virus (FeLV) was evaluated. The cellular immunity was evaluated by means of the lymphocyte transformations test (LTT), nitroblue-tetrazolium reduction test (NBT) and cytochrome C-reduction test (CRT). Mean value and standard deviation was calculated from the results. The significance was determined by the t-test. The animals were examined clinically daily for 20 days for the feline respiratory disease complex. When necessary, the animals were treated by homeopathic and antibiotic products. At the time of admission to the home all cats were or had been treated with an attenuated panleukopenia vaccine. The serologic parameters were not influenced in the cats of group I.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effectiveness of paramunization for the control of feline coryza]. 152 77

Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome reductase and xanthine oxidase are capable of transforming Adriamycin and forming free radicals. These reactive metabolites produce unwanted toxic side effects; however, their action may be partially ameliorated by the concomitant administration of thiols. In this study we evaluated the therapeutic activity of combinations of mesna (2-mercaptoethanesulfonate) with cyclophosphamide or Adriamycin in mice with a variety of transplantable tumors (L1210 and P-388 leukemia, Lewis lung and colon 26 carcinoma, B16 melanoma, and M5076 sarcoma). In all cases the administration of mesna prior to cyclophosphamide or Adriamycin treatment did not reduce the antitumor effectiveness of these agents and in some instances (C57BL/6 mice with B16 melanoma or M5076 sarcoma) small improvements were observed. Therefore, the addition of thiols, to reduce effectively the buildup of toxic metabolites of cyclophosphamide or Adriamycin may result in the improved therapeutic effectiveness for these agents in the treatment of cancer.
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PMID:Combinations of mesna with cyclophosphamide or adriamycin in the treatment of mice with tumors. 310 25

Sudan III treatment of Long-Evans rats results in increased hepatic monooxygenase activity using ethoxycoumarin and aniline as substrates. Monooxygenase activity towards amino-pyrine and nitrosodimethylamine is not affected. Sudan III treatment results in increased microsomal cytochrome P448 and increased amounts of a protein band which comigrates with purified cytochrome P448 during SDS polyacrylamide gel electrophoresis. The proportions of the different dihydrodiols formed during the incubation of 7,12-dimethylbenz[a]anthracene with microsomes vary between untreated and treated animals. Thus, extracts of microsomes from untreated rats were found to contain materials with chromatographic properties identical to those of the 3,4-dihydrodiol and the 5,6-dihydrodiol when examined on two different h.p.l.c. systems. Extracts of microsomes from Sudan III treated animals were found to contain materials with chromatographic properties identical to those of the 5,6-dihydrodiol and the 8,9-dihydrodiol when similarly examined. These findings suggest that the protective effect of Sudan III against DMBA induced leukaemia is mediated by an alteration in monooxygenase activity.
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PMID:Alterations in the metabolism of 7,12-dimethylbenz[a]anthracene and various xenobiotics by rat hepatic microsomes following Sudan III treatment in vivo. 391 57

The human HL-60 myeloid leukaemia cell line developed, during maturational changes induced by dimethyl sulphoxide, an enhanced capacity for phorbol myristate acetate- stimulated oxidative activity and acquired a cytochrome b. Titration of the absorbance at 559 nm at potentials of-190 to -370 mV indicated that this cytochrome had a very low potential, differentiating it from mitochondrial and endoplasmic reticulum cytochromes and identifying it as the cytochrome b(-245) that has been recently found in other phagocytic cells. Subcellular fractionation studies of mature HL-60 cells showed that cytochrome b had a dual distribution within the cell. The lighter peak of activity was associated with the plasma membrane markers, adenylate cyclase and receptors for the N- formal-L-methionyl-L-leucyl-L-phenylalanine (f-Met-Leu-Phe) peptide. The denser components localized with the mitochondria but were distinct from mitochondrial cytochromes because whereas the activity of cytochrome c oxidase fell during HL-60 cell maturation, that of this cytochrome b was markedly increased. Concentrations of myeloperoxidase were unrelated to activity of the oxidase system and decreased as the cell matured. The increase in the concentrations of cytochrome b with cellular maturation parallelled the increase in the stimulated nonmitochondrial respiratory activity of these cells. The turnover of the hexose monophosphate shunt of immature cells was increased by the oxidising agents, methylene blue and tert-butylhydroperoxide, indicating that these immature cells have stimulated nonmitochondrial respiratory activity by maturing HL-60 cells is associated with, and is probably dependent upon, the acquisition by these cells of the cytochrome b(-245) oxidase system.
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PMID:Development of cytochrome b and an active oxidase system in association with maturation of a human promyelocytic (HL-60) cell line. 629 56

The effects of some inducers of microsomal cytochrome P450-dependent monooxygenases on the metabolic bioactivation and the cytotoxicity of the antitumoral drug ellipticine (ELPT) were studied. Rate of growth of leukemia L1210 cells was measured in vitro in the absence and presence of ELPT or measured when the ELPT was metabolically transformed by noninbred Sprague-Dawley rat liver microsomes. The animals used were either untreated or pretreated by various inducers such as phenobarbital, 3-methylcholanthrene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin, Aroclor 1254, or ELPT. The transformation of ELPT into its two main metabolites, 9-hydroxyellipticine (9-OHE) and 7-hydroxyellipticine, was studied and measured by high-pressure liquid chromatography in conjunction with the determination of cytotoxic activity. A large variability was observed in the bioactivation and cytotoxic efficiency of ELPT mediated by the different microsomal preparations: The more P448 and/or P1-450 forms of cytochrome were induced, the more the 9-OHE was produced and the more the cytotoxicity toward L1210 cells was enhanced. These features were compared with those elicited by the activation of cyclophosphamide, which was transformed into cytotoxic metabolites by the cytochrome P450 form specifically induced by phenobarbital-type inducers.
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PMID:Influence of inducers of monooxygenases on cytotoxic efficiency of ellipticine on leukemia L1210 cells. 694 54

The Ah locus represents a complex "cluster" of genese controlling the induction of numerous drug-metabolizing enzyme "activities" by polycyclic aromatic compounds. Allelic differences at the Ah locus are reflected in the large differences in inducibility of cytochrome P1-450 and benzo[a]pyrene metabolism in numerous tissues when the mice receive the chemical daily in their diet. This experimental model system offers to the hematologist and clinical pharmacologist a means to study genetic differences in toxic chemical depression of the bone marrow, as well as a potential model to study aplastic anemia and leukemia explainable on a single-gene basis. The genetically "responsive" individual who is at increased risk for cancer caused by subcutaneous or topical or intratracheal polycyclic hydrocarbons is at decreased risk for toxicity of the bone marrow and leukemia caused by oral benzo[a]pyrene (when compared with the genetically "nonresponsive" individual receiving the same dose of the same xenobiotic). In other words, tissue sites in direct contact with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dose but the route of administration and the tissue in which the malignancy or toxicity develops are therefore very important in the interpretation of data from tumorigenesis or toxicity experiments involving P1-450 inducers such as polycyclic hydrocarbons. There exists sufficient evidence that heritable variation of the Ah locus occurs in man. Growing evidence indicates that persons with higher aryl hydrocarbon hydroxylase inducibility in their cultured mitogen-activated lymphocytes may have a statistically significantly increased risk for certain types of cancer and drug toxicity. It remains to be determined at the present time, however, whether this genotype can be used as a biochemical marker in the individual patient for predicting increased susceptibility to certain types of environmentally caused cancers or toxicity in man.
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PMID:Genetic differences in susceptibility to chemically induced myelotoxicity and leukemia. 701 19

Some monoepoxides of linoleic acid (LA) were converted to monochlorohydrins in low-pH solutions containing chloride ions (Cl-). Conversely, monochlorohydrins of LA were converted to monoepoxides in high-pH solutions. We attempted to determine whether these monochlorohydrins and monoepoxides were produced from LA by the cytochrome-c-H2O2-and/or myeloperoxidase-H2O2-system. The existence of monoepoxides and monochlorohydrins of LA in leukocytes was confirmed by high-performance liquid chromatography (HPLC). Furthermore, leukotoxin in human leukemia cells (THP-1) was stained immunohistochemically by a monoclonal anti-leukotoxin antibody.
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PMID:pH dependent alterations of monoepoxides and monochlorohydrins of linoleic acid, and their existence in vivo. 748 65

Cytochrome b558 composed of large and small subunits, and cytosolic 47- and 65-kDa proteins are important constituents of the superoxide (O2-) generating system in phagocytes and B lymphocytes. In this paper, we describe changes in O2(-)-generating activity and expression of O2(-)-generating components during differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. Undifferentiated U937 cells generated no O2- in response to a stimulation, although they expressed the three components other than the cytochrome b558 large subunit. When U937 cells were cultured with agents that induced the cell differentiation, such as vitamin D3, retinoic acid, interferon-gamma, and tumor necrosis factor, O2(-)-generating activity increased 5- to 200-fold depending on the agent used. Immunoblotting analysis revealed that the amounts of the four protein components essential for O2- generation increased, although their induction levels were significantly different between inducers. Among the four protein components, the cytochrome subunits were induced in low levels by all agents tested, which may explain why the O2(-)-generating activity of differentiated U937 cells was much lower than that of neutrophils from peripheral blood.
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PMID:Induction of essential components of the superoxide generating system in human monoblastic leukemia U937 cells. 788 47

The effects of three bisethyl polyamine analogs on mitochondrial structure and function were examined in human HeLa and L1210 murine leukemia cells. N, N' Bis-[3(ethylamino)-propyl]1-7- heptane diamine (BEPH), and its octane (BEPO), and butane (BESPM) derivative, were shown by electron microscopy and/or Rhodamine 123 uptake studies to alter the structural integrity of mitochondria when both cell lines were treated at the approximate IC50 dose of each drug. At this dose, BEPH had no marked effects on levels of the naturally occurring polyamines, putrescine, spermidine or spermine, in either cell line whereas BEPO and BESPM treatment did result in pool depletion. Southern blot analysis demonstrated a time and dose-dependent loss of mitochondrial DNA from BEPH-treated L1210 cultures suggesting that loss of mitochondrial integrity extended to the DNA level. Treatment of L1210 cells with all three analogs revealed marked reductions in the activity of two mitochondrial enzymes citrate synthase and cytochrome C oxidase. HeLa cells treated with all three analogs exhibited markedly reduced levels of ATP, complete loss of cytidine triphosphate (CTP) and near total depletion of uridine triphosphate (CTP) and near total depletion of uridine triphosphate (UTP). There was also a loss of colony forming ability in HeLa cells which could be nearly completely reversed by the addition of either uridine or cytidine suggesting that NTP reduction may be the primary antiproliferative determinant in these cells. Growth inhibition by BEPH in L1210 cells was markedly potentiated by the glycolysis inhibitor, 2-deoxyglucose, which had no such effect in otherwise untreated cells. This suggests that BEPH treatment of L1210 cells results in impairment of mitochondrial ATP synthesis and activation of the glycolytic pathway for energy production. 2-deoxyglucose treatment also completely prevented the increase of ATP by BEPH treatment of L1210 cells. It is concluded that all three bisethyl polyamines alter HeLa and L1210 mitochondria both structurally and functionally and that these alterations may play a primary role in the antiproliferative activity of these agents in HeLa cells. In L1210, the different spectra of cellular biochemical changes following bisethyl polyamine treatment suggests that additional mechanisms may be in effect.
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PMID:Anti-mitochondrial effects of bisethyl polyamines in mammalian cells. 801 33

Benzene, an important industrial solvent and constituent of unleaded gasoline, causes leukemia and aplastic anemia in humans. Mice are more sensitive than rats to benzene toxicity, though neither species has been shown to respond consistently with benzene-induced leukemia. Benzene biotransformation in liver to phenol, hydroquinone, catechol and/or muconaldehyde is thought to be necessary for its hematotoxicity and/or genotoxicity. Our goal is to develop a mathematical simulation model capable of describing the pathways and kinetics of benzene metabolism by rat and mouse liver microsomes and to assess the role of species metabolic differences in species sensitivity. Microsomes were incubated with 4 microM [U-14C]-benzene or 4 microM [U-14C]phenol. Metabolite production was quantified by extraction into ethyl acetate, HPLC separation and liquid scintillation spectroscopy. After 45 min, mouse liver microsomes converted 20% of the benzene to phenol, 31% to hydroquinone and 2% to catechol. Rat liver microsomes converted 23% of benzene to phenol, 8% to hydroquinone and 0.5% to catechol. Production of hydroquinone and catechol continued for 90 min for mouse liver microsomes, while production by rat liver microsomes had virtually ceased by 90 min. Muconic acid production by mouse liver microsomes was < 0.2% and < 0.04% from benzene and phenol respectively after 90 min. A quantitative simulation model was constructed to describe the in vitro metabolism of benzene, incorporating the reaction sequences: benzene-->phenol-->catechol-->trihydroxybenzene and phenol-->hydroquinone-->trihydroxybenzene. In the model, all of the reaction steps are assumed to be catalyzed by the same enzyme(s), cytochrome(s) P450, and benzene, phenol, hydroquinone and catechol in solution are all assumed to compete, through reversible binding, for the same reaction site(s) on cytochrome(s) P450. The simulation model accurately described both the benzene and phenol kinetic data, supporting this proposed mechanism. In particular, this model suggests that the observed inhibition of benzene on phenol metabolism, and of phenol on benzene metabolism, occurs through competition for a common reaction site, which can also bind catechol and hydroquinone.
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PMID:Benzene and phenol metabolism by mouse and rat liver microsomes. 826 15


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