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

Megakaryocytic cell lines, established from the blood of patients with leukaemia, provide us with a unique opportunity to study the proliferation, differentiation and maturation of megakaryocytes. Eighteen human and three animal cell lines that express some megakaryocytic features have been described in the literature. Many of these cell lines have primitive multiphenotypic properties of erythroid, myeloid and megakaryocytic cells, while some show more restricted megakaryocyte-specific markers. The most consistent cell marker of megakaryocytic cell lines is the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines and that of acetylcholinesterase in mouse or rat cell lines. The expressions of GPIb, von Willebrand factor and platelet peroxidase are variable among different cell lines, perhaps reflecting different stages of differentiation or a neoplastic nature of immortal cell lines. Treatment of many of these cell lines with phorbol esters leads to enhanced expression of the megakaryocytic programme.
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PMID:Megakaryocytic cell lines. 915 15

We have compared the singlet oxygen-mediated inactivation of acetylcholinesterase (ACE) in solution with the inactivation of ACE on the surface of K562 leukemia cells. In solution, the actions of the singlet-oxygen quenchers, methionine, azide, disodium [N,N'-ethylenebis (5-sulfosalicylideneimminato)]nickelate(II) (Ni-chelate 1) and disodium [(N,N'-2,3-propionic acid)bis(5-sulfosal-icylideneimminato)] nickelate(II) (Ni-chelate 2) could be explained quantitatively by assuming their only mechanism of action was to quench singlet oxygen. The singlet oxygen quenchers, azide, Ni-chelate 1 and Ni-chelate 2, caused smaller inhibitions in the rate of singlet oxygen-mediated inactivation of ACE on K562 cells than ACE in solution. The effects of these quenchers and of deuterium oxide were interpreted using a mathematical model of singlet-oxygen quenching and diffusion to estimate the lifetime of singlet oxygen near the cell surface. The azide quenching data and the deuterium-oxide data gave lifetimes of 0.9 +/- 0.2 microsecond and 0.45 +/- 0.15 microsecond, respectively. The increases in ACE inactivation lifetime caused by the nickel chelates were anomalously large. The unexpectedly large quenching due to the nickel chelates may have been due to a nonuniform distribution of the chelates in the cytoplasm with a large concentration of the chelate near the cell membrane.
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PMID:Singlet oxygen-mediated inactivation of acetylcholinesterase: a comparison of purified enzyme in solution and enzyme bound to K562 leukemia cells. 915 62

Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z,Z-muconaldehyde forms cyclic products containing a pyrrole residue linked to purine. Increased HbCO concentrations reduce the O2-carrying capacity of the blood, and the changed shape of the O2-Hb dissociation curve parallels disturbance in O2 unloading. CN- acts on electron transport and paralyses respiration. In telodrin poisoning, preconvulsive glutamine formation abstracts tricarboxylic acid intermediates incommensurately with normal cerebral respiration. Antigen-antibody complexing depletes the antibody titre, available against infection. At high doses of Cd, Cd-thionein filtered through the kidneys is reabsorbed and tubular lesions produced. Some organophosphate insecticides promote irreversible acetylcholinesterase phosphorylation and blockade nerve function, and others react with neurotoxic esterase to cause delayed neuropathy. The evidence for Paraquat pulmonary poisoning suggests a radical mechanism involving three interrelated cyclic reaction stages. The action of N- and O8 (O substituent in 6-position of the purine) demethylases explains deletion mechanisms for DNA-alkyl adducts. DNA-directed synthesis in the presence of ultimate carcinogens provides for an estimation of misincorporations, which implicate the same transversions as those found by direct mutagenicity testing. Chemical carcinogens recognize tissue-sensitive cells and modify their heritable genetic complement. Oncoproteins encoded by activated oncogenes signal the transformation of normal cells into cancer cells. The importance of the H-ras oncogene and p53 tumour-suppressor gene is stressed. Antidotal action is analysed; for example, parenteral glutamine administration to telodrin-intoxicated rats restores the depleted cerebral glutamate level and prevents seizures. Glutamate acts as anticonvulsant in petit mal epilepsy. In general, therefore, the reaction of the toxicant-related substance with the relevant target-tissue macromolecule accounts for the biochemical/biological events at a cellular level a
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PMID:Toxic action/toxicity. 1074 Aug 94

Tris(2-chloroethyl) phosphate (TRCP), a flame-retardant plasticizer used in plastics, polymeric foams, and synthetic fibers, was studied as part of the National Toxicology Program's class study of trisalkyl phosphate flame retardants. Toxicology and carcinogenesis studies were conducted by administering TRCP (approximately 98% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 16 weeks, or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. 16-Day Studies: There were no chemical-related deaths, differences in final mean body weight, or histopathological lesions in rats receiving 22 to 350 mg/kg TRCP or in mice receiving 44 to 700 mg/kg TRCP for 12 doses over 16 days. Serum cholinesterase activity in female rats receiving 175 or 350 mg/kg TRCP was reduced slightly (80% of control levels), but enzyme activity in dosed male rats and in mice was similar to that in controls. 16-Week Studies: Rats received 22 to 350 mg/kg TRCP for 16 weeks (female) or 18 weeks (male). Several male and female rats in the 175 or 350 mg/kg dose groups died from chemical toxicity. Final mean body weights of female rats receiving 350 mg/kg were 20% greater than those of controls; final mean body weights of the remaining groups of dosed female rats and dosed male rats were similar. Chemical-related neuronal necrosis occurred in the hippocampus and thalamus of female rats and, to a lesser extent, of male rats. Serum cholinesterase activity was reduced in females receiving 175 or 350 mg/kg TRCP. There were no chemical-related deaths, differences in final mean body weight, or differences in cholinesterase activity in mice receiving 44 to 700 mg/kg TRCP for 16 weeks. Tubule epithelial cells with enlarged nuclei (cytomegaly and karyomegaly) were observed in the kidneys of high-dose (700 mg/kg) male and female mice. 2-Year Studies: The 2-year studies in rats were conducted by administering 0, 44, or 88 mg/kg TRCP to groups of 60 males and females, 5 days per week for up to 104 weeks; 9 or 10 rats of each dose group were evaluated at 66 weeks. The survival of high-dose male and female rats was reduced relative to that of controls. Final mean body weights of surviving rats were similar to those of controls. The principal chemical-related effects occurred in the kidney and brain of dosed rats. Focal hyperplasia of the renal tubule epithelium and renal tubule adenomas were markedly increased in male rats receiving 88 mg/kg TRCP and, to a lesser extent, in female rats (renal tubule hyperplasia, male rats: 0/50; 2/50; 24/50; female rats: 0/50; 3/50; 16/50; renal tubule adenoma, male rats: 1/50; 5/50; 24/50; female rats: 0/50; 2/50; 5/50). Renal tubule carcinomas occurred in one control and one high-dose male rat. Degenerative lesions consisting of gliosis, mineralization, hemorrhage, and/or hemosiderin accumulation occurred in the cerebrum and brain stem of more than 50% of female rats receiving 44 or 88 mg/kg TRCP; similar lesions were seen in only a few dosed males. Slightly increased incidences of thyroid gland follicular cell neoplasms (male rats: 5/50; 14/50; 13/50; female rats: 14/50; 16/50; 20/50) occurred in dosed males and females, but it is uncertain whether these were related to chemical administration. The 2-year studies in mice were conducted by administering 0, 175, or 350 mg/kg TRCP to groups of 60 males and females, 5 days per week for up to 104 weeks; 8 to 10 mice of each sex per dose group were evaluated at 66 weeks. There were no significant differences in survival between dosed and control groups of either sex, and final mean body weights of mice were similar among all groups. The principal chemical-related effects occurred in the kidney, in which nuclear enlargement (karyomegaly) of tubule epithelial cells was present in approximately 80% of high-dose mice. In the original diagnosis, renal tubule adenomas were seen in one control male, one high-dose male, and one low-dose female. A carcinoma was also seen in one high-dose male. In a s seen in one high-dose male. In a subsequent examination of step sections of all the mouse kidneys, adenomas were found in one low-dose male and two high-dose males. The incidences of renal tubule neoplasms in the original and step sections combined were 1/50, 1/50, and 4/50 for males. Female mice receiving TRCP demonstrated a marginally increased incidence of neoplasms (primarily adenomas) of the harderian gland (3/50; 8/50; 7/50); in addition, three harderian gland neoplasms occurred in high-dose female mice evaluated after 66 weeks. Genetic Toxicology: TRCP was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98 with or without exogenous metabolic activation (S9), and it tested negative for the induction of chromosomal aberrations in Chinese hamster ovary (CHO) cells. TRCP produced an equivocal response in the presence of S9 for the induction of sister chromatid exchanges (SCE) in CHO cells. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity for male and female F344/N rats receiving tris(2-chloroethyl)phosphate as shown by increased incidences of renal tubule adenomas. Thyroid follicular cell neoplasms and mononuclear cell leukemia in male and female rats may have been related to chemical administration. There was equivocal evidence of carcinogenic activity for male B6C3F1 mice as shown by a marginally increased incidence of renal tubule cell neoplasms. There was equivocal evidence of carcinogenic activity for female B6C3F1 mice as shown by a marginally increased incidence of harderian gland adenomas. Renal tubule cell hyperplasia in male and female rats and gliosis, hemorrhage, pigmentation (hemosiderin accumulation), and mineralization in the brains of female rats were associated with the administration of tris(2-chloroethyl) phosphate. Karyomegaly of renal tubule epithelial cells in male and female mice was also chemical related. Synonyms: 2-chloroethanol phosphate (3:1); tris(b-chloroethyl) phosphate Trade Names: Fyrol CEF; Disflamoll TCA; NIAX flame retardant
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PMID:NTP Toxicology and Carcinogenesis Studies of Tris(2-chloroethyl) Phosphate (CAS No. 115-96-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1263 68

Acetylcholinesterase (AChE - EC. 3.1.1.7) plays an essential role in acetylcholine-mediated neurotransmission. Unfortunately, an AChE-peptide exhibits pathophysiological activity via an apoptotic pathway that could play an important role in neuronal development and neurodegeneration. It was found that a peptide derived from AChE may induce neuronal death and acetylcholinesterase may induce neurological changes in the development of Alzheimer's disease. It was also stated that complex of AChE with beta-amyloid is much more toxic than amyloid and causes stronger neurological changes. AChE promotes the generation of amyloid by accelerating the expression of peptide precursor (beta-APP) in glial cells. The essential role is also played by AChE in induction of hematological disease. It is well known that phospho-organic compounds cause inhibition of AChE precursors what is related to decrease of hemoglobin concentration, number of erythrocytes and hematocrit level. The article is an attempt to explain the role of acetylcholinesterase in neuronal apoptosis, Alzheimer's disease and Myasthenia gravis as well as in leukemia.
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PMID:[Acetylcholinesterase--apoptosis induction, role in neurological diseases and leukemia]. 1620 53

Hematological changes induced by various stress stimuli are accompanied by replacement of the primary acetylcholinesterase (AChE) 3' splice variant acetylcholinesterase-S (AChE-S) with the myelopoietic acetylcholinesterase-R (AChE-R) variant. To search for putative acetylcholinesterase-S interactions with hematopoietic pathways, we employed a yeast two-hybrid screen. The transcriptional co-repressor C-terminal binding protein (CtBP) was identified as a protein partner of the AChE-S C terminus. In erythroleukemic K562 cells, AChE-S displayed nuclear colocalization and physical interaction with CtBP. Furthermore, co-transfected AChE-S reduced the co-repressive effect of CtBP over the hematopoietic transcription factor, Ikaros. In transgenic mice, overexpressed human (h) AChE-S mRNA induced selective bone marrow upregulation of Ikaros while suppressing FOG, another transcriptional partner of CtBP. Transgenic bone marrow cells showed a correspondingly elevated potential for producing progenitor colonies, compared with controls, while peripheral blood showed increased erythrocyte counts as opposed to reduced platelets, granulocytes and T lymphocytes. AChE's 3' alternative splicing, and the corresponding changes in AChE-S/CtBP interactions, thus emerge as being actively involved in controlling hematopoiesis and the potential for modulating immune functions, supporting reports on malfunctioning immune reactions under impaired splice site selection.
Leukemia 2007 Jul
PMID:Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia. 1747 78

Ionic liquids are widely studied as alternative solvents in organic synthesis and catalysis, in electrochemistry and the separation sciences; with their many applications they will soon be produced on an industrial scale. Available toxicological data of ionic liquids have already suggested initial guidelines for the conscious design of safer chemicals. In this study a new group of such redesigned ionic liquids-1-alkoxymethyl-3-hydroxypyridinium cations+acesulphamate, saccharinate and chloride anions-was assayed with respect to their inhibitory activity towards acetylcholinesterase and their cellular toxicity towards the IPC-81 rat promyelocytic leukaemia cell line: the acute biological activity of these compounds is very low. Effective concentrations lie in the millimole range, which is well above possible intracellular concentrations. Only the compounds with the longest alkoxymethyl chain inhibit the enzyme at effective concentrations that are one order of magnitude smaller. No significant differences are observed when the anion compartment in the enzymatic assay is varied. However, the cytotoxicity data show EC(50) for acesulphamates and saccharinates to be higher than the values for the chloride analogues. Also, a slight alkoxymethyl chain length effect on the overall cytotoxicity is discernible. The biodegradability of the 1-alkoxymethyl-3-hydroxypyridinium salts varies from 21% to 72% and depends on the type of anion the cation is linked with. It improves with lengthening alkyl chain, but only in the range from 4 to 11 carbon atoms.
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PMID:Assessing toxicity and biodegradation of novel, environmentally benign ionic liquids (1-alkoxymethyl-3-hydroxypyridinium chloride, saccharinate and acesulfamates) on cellular and molecular level. 1791 19

Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. Recently, numerous biological activities such as cytotoxic effect on leukemia cells, and antitumor, neuroprotection, and antibacterial activities have been reported for this compound. Although a number of proteins including protein kinase C, androgen receptor, and acetylcholinesterase were proposed as molecular targets responsible for the activities of decursinol, they are not enough to explain such a diverse biological activity mentioned above. In this study, we employed a chemical proteomic approach, leading to identification of seven proteins as potential proteins interacting with decursinol. Most of the proteins contain a defined ATP or nucleic acid binding domain and have been implied to be involved in the pathogenesis and progression of various human diseases including cancer, autoimmune disorders, or neurodegenerative diseases. The present results may provide clues to understand the molecular mechanism of the biological activities shown by decursinol, an anticancer natural product.
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PMID:Identification of proteins binding to decursinol by chemical proteomics. 1875 4

In this study, seeds of Lycopersicon esculentum Mill. were analyzed by HPLC/UV-PAD/MS(n)-ESI. Fourteen flavonoids were identified, including quercetin, kaempferol, and isorhamnetin derivatives, with 13 of them being reported for the first time in tomato seeds. The major identified compounds were quercetin-3-O-sophoroside, kaempferol-3-O-sophoroside, and isorhamnetin-3-O-sophoroside. A significant cell proliferation inhibition (>80%), against rat basophile leukemia (RBL-2H3) cell line, was observed with this extract (IC(50) = 5980 microg/mL). For acetylcholinesterase inhibitory activity, a concentration-dependent effect was verified (IC(20) = 2400 microg/mL). The same behavior was noted regarding antioxidant capacity, evaluated against DPPH (IC(10) = 284 microg/mL), nitric oxide (IC(25) = 396 microg/L), and superoxide radicals (IC(25) = 3 microg/mL).
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PMID:Tomato ( Lycopersicon esculentum ) seeds: new flavonols and cytotoxic effect. 2013 41

Organophosphorus pesticide (OPP) toxicity is believed to be mediated through inhibition of acetylcholinesterase (AChE). Given their widespread distribution in aquatic systems and their ability to undergo chemical transformation, their environmental impacts at sublethal concentrations in nontarget organisms have become an important question. We conducted a number of mammalian-cell genotoxic and gene expression assays and examined cellular biochemical changes that followed low-dose exposure of MCF-7 cells to fenitrothion, diazinon, and the aqueous degradate of diazinon, 2-isopropyl-6-methyl-4-pyrimidinol (IMP). After exposure to the OPPs at low concentrations (10(-12) M to 10(-8) M), greater than twofold elevations in micronucleus formation were noted in MCF-7 cell cultures that went on to exhibit greater than 75% clonogenic survival; these levels of chromosomal damage were comparable to those induced by 10(-6) M benzo[a]pyrene, a known genotoxic agent. At this low concentration range, a fenitrothion-induced twofold elevation in B-cell leukemia/lymphoma-2 (BCL-2) and cytochrome P450 isoenzyme (CYP1A1) gene expressions was observed. Principal component analysis-linear discriminant analysis (PCA-LDA) of derived infrared (IR) spectra of vehicle control (nonexposed) and OPP-exposed cells highlighted that both fenitrothion and diazinon induced marked biochemical alterations in the lipid, protein, and DNA/RNA absorbance regions. Our findings demonstrate that the two OPP parent chemicals and IMP degradate can mediate a number of toxic effects or cellular alterations at very low concentrations. These are independent of just selective inhibition of AChE, with potential consequences for nontarget organisms exposed at environmentally relevant concentrations. Further assays on relevant aquatic organism cell lines are now recommended to understand the mechanistic low-dose toxicity of these chemicals present in aquatic systems.
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PMID:Sublethal genotoxicity and cell alterations by organophosphorus pesticides in MCF-7 cells: implications for environmentally relevant concentrations. 2129 9


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