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

Epidemiological studies of occupational exposure to formaldehyde gas (HCHO) have suggested possible links between concentration and duration of exposure, and elevated risks of leukaemia and other cancers at sites distant from the site of contact. Formaldehyde is a highly water soluble gas which, when inhaled, reacts rapidly at the site of contact and is quickly metabolised by enzymes in the respiratory tissue. Inhaled formaldehyde is almost entirely absorbed in the respiratory tract and, for formaldehyde induced toxicity to occur at distant sites, HCHO must enter the blood and be transported to systemic tissues via the circulatory system. A mathematical model describing the absorption and removal of inhaled formaldehyde in the nasal tissue is therefore formulated to predict the proportion of formaldehyde entering into the blood. Accounting for the spatial distribution of the formaldehyde concentration and the metabolic activity within the mucosa, the concentration of formaldehyde in the mucus, the epithelium and the blood has been determined and was found to attain a steady-state profile within a few seconds of exposure. The increase of the formaldehyde concentration in the blood was predicted to be insignificant compared with the existing pre-exposure levels in the body, indicating that formaldehyde is rapidly removed in the nasal tissue. The results of the model thus suggest that it is highly unlikely that following inhalation by the nose, formaldehyde itself will cause toxicity at sites other than the initial site of contact in the respiratory tract.
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PMID:A mathematical model for the absorption and metabolism of formaldehyde vapour by humans. 1603 42

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent's potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will be published as Volume 88 of the IARC Monographs.
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PMID:Meeting report: summary of IARC monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. 1614 Jun 28

The mitochondria-specific dyes, TMRE, H2-CMX-Ros and MTR580 were determined for their suitability to measure mitochondrial potential changes of the T cell leukemia cell line Jurkat and insulin-secreting beta cell line NIT-1 during apoptosis. Both freshly harvested Jurkat and NIT-1 cells induced to undergo apoptosis displayed poor retention of the potential-sensitive, intrinsically fluorescent dye, TMRE. Treatment with formaldehyde or paraformaldehyde completely abolished TMRE uptake in both cell types regardless of apoptosis induction. Interestingly, freshly harvested apoptotic Jurkat cells exhibited lower retention of H2-CMX-Ros, indicating marked reduction in the oxidative status of lymphoid cells during apoptosis. This is in contrast to NIT-1 cells which failed to display significant reduction in H2-CMX-Ros retention after anoikis induction. Paraformaldehyde treatment reduced the retention of H2-CMX-Ros in live Jurkat cells but still allowed the discrimination of apoptotic cells which poorly retained H2-CMX-Ros. However, live Jurkat cells lost their ability to retain H2-CMX-Ros after formaldehyde treatment. In contrast, treatment with paraformaldehyde or formaldehyde did not have significant impact on the retention of H2-CMX-Ros in both live and apoptotic NIT-1 cells. The uptake of MTR580 was independent of mitochondrial membrane potential in both T and beta cell lines. However, MTR580 was comparable to H2-CMX-Ros for confocal microscopic analysis of apoptotic Jurkat cells following fixation with formaldehyde and cell permeabilization. These data demonstrate that while TMRE and H2-CMX-Ros are suitable for determining mitochondrial membrane potential changes during apoptosis in lymphoid cells, only TMRE is suitable for such analysis in beta cells. Both H2-CMX-Ros and MTR580 proved to be suitable for confocal imaging of mitochondria.
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PMID:Flow cytometric determination of mitochondrial membrane potential changes during apoptosis of T lymphocytic and pancreatic beta cell lines: comparison of tetramethylrhodamineethylester (TMRE), chloromethyl-X-rosamine (H2-CMX-Ros) and MitoTracker Red 580 (MTR580). 1625 33

A drug delivery system based on spontaneous deposition of soluble, low-molecular-weight therapeutic agents has been developed for the purpose of sustaining drug release. Layer-by-layer assembly of oppositely charged polyelectrolytes onto melamine formaldehyde (MF) colloidal particles, followed by removal of the cores at low pH has yielded intact hollow microcapsules having the ability to induce deposition of various water-soluble substances. Dynamic observation by confocal laser scanning microscopy provided direct evidence of such deposition. Dependence of loading rate on molecular weight was investigated. Efficient loading of an anti-cancer drug, daunorubicin (DNR), was confirmed by transmission electron microscopy (TEM). Its release was quantified by fluorometry. The results indicated that loading, and subsequent release, could be tuned by factors such as feeding concentrations, temperature, and salt concentrations. The intrinsic mechanism of loading and release was discussed taking into account the interaction between the drugs and the poly(styrene sulfonate)/MF complex existing in the hollow capsules. With culture of the HL-60 cell line, a kind of human leukemia cell, the presence of DNR-loaded capsules was seen to steadily decrease the cyto-viability. Fluorescence intensity averaged from inside the circles as a function of incubation time.
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PMID:Multilayer microcapsules as anti-cancer drug delivery vehicle: deposition, Sustained release, and in vitro bioactivity. 1630 33

A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC(50)<1 microM. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC(50) values of 0.74 and 0.34 microM, respectively.
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PMID:4-Methylideneisoxazolidin-5-ones--a new class of alpha-methylidene-gamma-lactones with high cytostatic activity. 1631 98

The International Agency for Research on Cancer (IARC, 2004) recently reevaluated the epidemiological data on formaldehyde and concluded that there was "strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to formaldehyde." This conclusion was tempered since a mechanism for leukemia induction could not be identified. Chemically induced leukemia is a well-studied phenomenon with benzene and a number of cancer chemotherapeutic drugs recognized as capable of causing this effect. Abundant in vitro and in vivo data in animals and humans demonstrate that exposure to sufficient doses of these recognized leukemogens can initiate a cascade of events leading to hematopoietic toxicity and the subsequent development of leukemia. This review addresses the biological plausibility that formaldehyde might be capable of causing any type of leukemia by providing a broad overview of the scientific data that must be considered in order to support or refute a conclusion that a particular substance might be leukemogenic. Data on benzene and selected chemotherapeutic cancer drugs are used as examples and are briefly summarized to demonstrate the similar biological events thought to result in leukemogenesis. These data are compared and contrasted with the available data on formaldehyde in order to judge whether they fulfill the criteria of biological plausibility that formaldehyde would be capable of inducing leukemia as suggested by the epidemiological data. Based on the epidemiological data, it is reasonable to expect that if formaldehyde was capable of inducing leukemia, in vivo and in vitro data would offer supporting evidence for biological plausibility. In particular, there is (1) no evidence to suggest that formaldehyde reaches any target organ beyond the site of administration including the bone marrow, (2) no indication that formaldehyde is toxic to the bone marrow/hematopoietic system in in vivo or in vitro studies, and (3) no credible evidence that formaldehyde induces leukemia in experimental animals. As discussed in this review, based on the key biological events that occur in the process of chemically induced leukemia, there is inadequate biological evidence currently available to corroborate existing weak epidemiological associations. This provides an insufficient database to conclude that there is a causal relationship for formaldehyde and leukemia risk.
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PMID:Formaldehyde as a potential human leukemogen: an assessment of biological plausibility. 1673 40

When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United States, a pattern of complaints emerged characterised by seven "key symptoms." Later, carefully controlled volunteer studies did not confirm the existence of the specific key symptoms, although one study of self-reported sensitive (SRS) people did suggest that a threshold at about 11-15% MTBE in gasoline may exist for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies on volunteers, including SRSs, found no adverse responses associated with MTBE at likely exposure levels. MTBE is well and rapidly absorbed following oral and inhalation exposures. Cmax values for MTBE are achieved almost immediately after oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated, either by exhalation as unchanged MTBE or by urinary excretion of its less volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other primary metabolite, formaldehyde, is detoxified at a rate very much greater than its formation from MTBE. MTBE has no specific effects on reproduction or development, or on genetic material. Neurological effects were observed only at very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol (included as an endogenous precursor of formaldehyde, without the presence of TBA), some increases in tumor incidence have been observed, but consistency of outcome was lacking and even some degree of replication was observed in only three cases, none of which had human relevance: alpha(2u)-globulin nephropathy-related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats, but not in mice, which provide the better model of the human disease; and B-cell-derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of orally dosed female rats. In addition, hepatocellular adenomas were significantly higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in female B6C3F1 mice treated with TBA, but these results lack any independent confirmation, which would have been possible from a number of other studies.
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PMID:Methyl tertiary-butyl ether: studies for potential human health hazards. 1680 2

Following antigen preparation procedures similar to those of the direct agglutination test (DAT), an IgG ELISA employing intact beta-mercaptoethanol (beta-ME)-treated Leishmania donovani promastigotes was developed. The performance of the beta-ME ELISA thus developed was assessed in patients with confirmed visceral leishmaniasis (VL), revealing slightly lower sensitivity (39/40=97.5%) than that of the DAT (40/40=100%). When challenged with sera of individuals with non-VL conditions, including leukaemia and African trypanosomiasis, the specificity of the beta-ME ELISA was 100% (158/158), compared to 98.8% (156/158) for DAT. In an endemic population (n=145) manifesting a clinical suspicion of VL, results obtained with the beta-ME ELISA were highly concordant with those of DAT, both in the seropositive (65/68=95.6%) and seronegative (77/80=96.3%) groups. Furthermore, the incorporated intact antigen demonstrated higher sensitivity in ELISA (16/18=88.9%) than the water-soluble equivalent (13/18=72.2%). The stability of the formaldehyde-fixed antigen (2 months at 4 degrees C) in beta-ME ELISA, as well as the option for direct testing of whole-blood samples and visual reading of results (within 2 h, compared to 18 h for DAT), advocate the simultaneous application of the technique with DAT for confirmation of VL in laboratories with limited facilities.
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PMID:Beta-mercaptoethanol-modified ELISA for diagnosis of visceral leishmaniasis. 1691 48

The mechanism of doxorubicin is compared with that of doxazolidine, a doxorubicin-formaldehyde conjugate. The IC(50) for growth inhibition of 67 human cancer cell lines, but not cardiomyocytes, is 32-fold lower with doxazolidine than with doxorubicin. Growth inhibition by doxazolidine correlates better with growth inhibition by DNA cross-linking agents than with growth inhibition by doxorubicin. Doxorubicin induces G2/M arrest in HCT-116 colon cancer cells and HL-60 leukemia cells through a well-documented topoisomerase II dependent mechanism. Doxazolidine fails to induce a G2/M arrest in HCT-116 cells but induces apoptosis 4-fold better than doxorubicin. The IC(50) for doxazolidine growth inhibition of HL-60/MX2 cells, a topoisomerase II deficient derivative of HL-60 cells, is 1420-fold lower than the IC(50) for doxorubicin, and doxazolidine induces apoptosis 15-fold better. Further, doxazolidine has little effect in a topoisomerase II activity assay. These data indicate that doxorubicin and doxazolidine induce apoptosis via different mechanisms and doxazolidine cytotoxicity is topoisomerase II independent.
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PMID:Doxazolidine induction of apoptosis by a topoisomerase II independent mechanism. 1769 16

A multicomponent reaction of indane-1,3-dione, an aldehyde and an amine-containing aromatic compound leading to the formation of indenopyridine-based heterocyclic medicinal scaffolds has been investigated. It was found that the yields significantly improve when oxygen gas is bubbled through the reaction mixture, facilitating the oxidation of the intermediate dihydropyridine-containing compounds to their aromatic counterparts. Investigation of the reaction scope revealed that formaldehyde, as well as various aliphatic, aromatic and heteroaromatic aldehydes, works well as the aldehyde component. In addition, substituted anilines and diverse aminoheterocycles can be utilized in this process as the amine-containing component. Preliminary biological evaluation of the synthesized library identified a pyrimidine-based polycycle, which rivals the anticancer drug etoposide in its toxicity and apoptosis inducing properties toward a human T-cell leukemia cell line.
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PMID:Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties. 1800 68


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