Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic exposure to high concentrations of benzene can result in the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving high frequency of loss of all or part of chromosomes 5 and/or 7 as well as trisomy 8. The pattern of reoccurring chromosome abnormalities associated with the development of leukemia can be used as a guide in understanding the etiology and pathogenesis of these diseases. Therefore, a research project was designed to determine whether a metabolite of benzene, hydroquinone (HQ), could directly induce loss of chromosome 5 and/or 7 and gain of chromosome 8. Using fluorescence in situ hybridization with chromosome-specific 5, 7 and 8 probes we demonstrate that 42, 49 and 26 microM HQ induces monosomy 5, 7 and 8, respectively, in the human lymphoblast cell line GM09948. These results demonstrate for the first time that HQ induces a specific chromosome loss found in secondary MDS/AML. The pattern of chromosome 5 and/or 7 loss in benzene-induced MDS/AML is probably due to selective cell survival after HQ exposure rather than specific targeting of HQ for chromosomes 5 or 7.
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PMID:The benzene metabolite, hydroquinone, induces dose-dependent hypoploidy in a human cell line. 930 10

Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving loss of all or part of chromosomes 5 and/or 7 as well as trisomy 8 and we have previously reported that hydroquinone (HQ) induces deletions of 5, 7 and 8. Benzene metabolism is a requirement for bone marrow toxicity and the phenolic metabolites, HQ and catechol (CAT), have been implicated in benzene hematotoxicity. A research project was designed to determine whether CAT by itself and in conjunction with HQ could directly induce loss of chromosome 5 and/or 7 and gain of chromosome 8. Using fluorescence in situ hybridization with chromosome-specific 5, 7, and 8 probes we demonstrate that 5 to 150 uM CAT does not produce chromosomal aberrations, however CAT and 25 uM HQ can act in synergy to induce dose dependent loss of these chromosomes. In addition HQ/CAT selectively induces -5q which is not observed for HQ only. These results demonstrate for the first time that CAT/HQ act in synergy to induce specific chromosome loss found in secondary MDS/AML.
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PMID:The benzene metabolites hydroquinone and catechol act in synergy to induce dose-dependent hypoploidy and -5q31 in a human cell line. 1070 50

Hydroquinone is a myelotoxin that is found in many foods and is also formed through the metabolism of benzene. Human exposure to benzene is associated with the development of myelodysplastic syndrome and acute myelogenous leukemia. Hydroquinone is genotoxic in several in vitro and in vivo test systems, inducing micronuclei (MN), sister-chromatid exchange (SCE), and chromosomal aberrations. Glutathione S-transferases (GSTs) are a superfamily of polymorphic enzymes involved in the conjugation of reactive chemical intermediates to soluble forms. These enzymes play a key role in the detoxification of endogenous and exogenous compounds, and the polymorphic genes GSTM1, GSTT1, and GSTP1 have been associated with the differential metabolism of several genotoxicants. In the present study, we have evaluated the effect of GSTM1, GSTT1, and GSTP1 polymorphisms on the frequency of MN and SCE induced by hydroquinone in human lymphocytes. Lymphocytes were obtained from 15 healthy non-smoking donors, and their GSTM1, GSTT1, and GSTP1 genotypes determined. Treatment of cultures of the lymphocytes with hydroquinone significantly increased the overall frequencies of MN and SCE (P<0.0001). Individuals with the GSTM1 null genotype had a significantly higher frequency of MN compared with GSTM1-present individuals (P=0.013); in contrast, the GSTM1 genotype had no effect on hydroquinone-induced SCE frequency. The other polymorphisms did not significantly affect the frequencies of MN or SCE. These results suggest that GSTM1 is involved in the metabolic fate of hydroquinone and that polymorphisms in GSTM1 could be related to inter-individual differences in DNA damage arising from the exposure to this compound.
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PMID:GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes. 1514 65

Alpha-cyclodextrin (alpha-CD) with an amino group was conjugated to an alpha, omega-dicarboxylated poly(ethylene glycol) (PEG). The inhibition constant (Ki) of the alpha-CD-PEG conjugate for the catalysis by beta-amylase was larger than that of alpha-CD, due to a steric obstruction of the PEG moiety to the binding of alpha-CD moiety to beta-amylase. alpha-CD-PEG was further modified with cystamine (CD-PEG-Cys) or cysteamine methyl disulfide (CD-PEG-MDS), and the disulfide-carrying alpha-CD-PEG was accumulated on a gold surface as a self-assembled monolayer (SAM). The binding of beta-amylase to the alpha-CD-PEG SAM was followed by a decrease in cathodic peak current in the voltammogram of hydroquinone as a probe using a cyclic voltammetry (CV). The beta-amylase bound to the alpha-CD-PEG SAM was desorbed by the addition of free alpha-CD, and the ratio of desorbed beta-amylase from the SAM of alpha-CD-PEG-Cys to the total amount of the enzyme bound to the SAM was 40% whereas that from the alpha-CD-PEG-MDS SAM was 83-85%. The percentage of desorption was increased to 100% by the treatment of the alpha-CD-PEG-MDS SAM-carrying electrode with 2-hydroxyethyldisulfide prior to the immersion in the enzyme solution. Adsorption and desorption processes of beta-amylase to the surface of alpha-CD-PEG-MDS SAM were clearly observed using localized surface plasmon resonance absorption spectroscopy. The binding constant of the enzyme to the surface-confined alpha-CD-PEG was much larger than that to free alpha-CD, probably due to a large local concentration of the alpha-CD moiety on the gold surface.
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PMID:Fishing of beta-amylase with a SAM of alpha-cyclodextrin-poly- (ethylene glycol) conjugate. 1546 7

Hydroquinone is a phenolic metabolite of benzene, a known human carcinogen. Hydroquinone is widely used in the industry. We report a case of a 43-year-old male diagnosed with antecedent myelodysplastic syndrome and acute myeloid leukemia following 16 years of occupational exposure to hydroquinone in radiographic developer solution. Cytogenetic studies revealed aberrations in chromosome 5 and chromosome 7. We review the literature on hydroquinone as a potential cause of hematolymphatic cancers and discuss the role of hydroquinone as a genotoxic and leukemogenic agent.
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PMID:Hydroquinone, a benzene metabolite, and leukemia: a case report and review of the literature. 2151 98