Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells
Martyn T. SmithLuoping ZhangMichael JengYunxia WangWeihong GuoPaurene DuramadAlan HubbardGuenther HofstadlerNina Holland
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Abstract:
Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34 + cells). In this study, human cord blood, which is particularly rich in CD34 + cells, was exposed to hydroquinone for 72 h in a medium that favored CD34 + cell survival and growth. CD34 + and CD34 – cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34 + cells were generally more susceptible to aneusomy induction by hydroquinone than CD34 – cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34 + cells ( Ptrend < 0.001), whereas in CD34 – cells only an increased level of monosomy 7 was detected ( Ptrend = 0.002). Particularly striking effects of hydroquinone were observed in CD34 + cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34 + cells play a role in benzene-induced leukemogenesis.Keywords:
Hydroquinone
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Bone marrow derived progenitor cells participate in the repair of injured vessels. The lungs of individuals with emphysema have reduced alveolar capillary density and increased endothelial apoptosis. We hypothesized that circulating levels of endothelial and hematopoietic progenitor cells would be reduced in this group of patients.The goal of this study was to measure circulating levels of endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) in subjects with COPD and to determine if progenitor levels correlated with disease severity and the presence of emphysema.Peripheral blood mononuclear cells were isolated from 61 patients with COPD and 32 control subjects. Levels of EPCs (CD45(dim) CD34+) and HPCs (CD45(+) CD34(+) VEGF-R2(+)) were quantified using multi-parameter flow cytometry. Progenitor cell function was assessed using cell culture assays. All subjects were evaluated with spirometry and CT scanning.HPC levels were reduced in subjects with COPD compared to controls, whereas circulating EPC levels were similar between the two groups. HPC levels correlated with severity of obstruction and were lowest in subjects with severe emphysema. These associations remained after correction for factors known to affect progenitor cell levels including age, smoking status, the use of statin medications and the presence of coronary artery disease. The ability of mononuclear cells to form endothelial cell colony forming units (EC-CFU) was also reduced in subjects with COPD.HPC levels are reduced in subjects with COPD and correlate with emphysema phenotype and severity of obstruction. Reduction of HPCs may disrupt maintenance of the capillary endothelium, thereby contributing to the pathogenesis of COPD.
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To determine the effects of recombinant human FLT3 ligand (rhFL) on in vitro expansion of human cord blood CD34+ cells.Human cord blood CD34+ cells were enriched by using a magnetic cell isolation system. CD34+ cells were incubated in liquid culture in the presence of different cytokines. The total number of all cells and the number of CD34+ cells and hematopoietic progenitor cells (CFU-GM and BFU-E) were counted at various time intervals.Human cord blood CD34+ cells could be enriched to the purity of more than 80%. The number of CD34+ cells increased 3.4 folds in the presence of rhFL + IL3 + IL6 + GMCSF + EPO in seven days, while in the control group without rhFL, it increased 1.5 folds. The difference of the number of more matured hematopoietic progenitor cells in the CD34+ cell population between the control group and the rhFL group was not significant.Only the primitive hematopoietic progenitor cells are expanded by rhFL according to the results obtained in the exclusion method.
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This study was undertaken to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on peripheral blood (PB) CD34+ progenitor cells during remission induction treatment in 11 children with newly diagnosed acute leukemia (7 with ALL, 4 with AML) whose bone marrow (BM) cells expressed fewer than 5% CD34 at the time of diagnosis. All children who had no infection were given HDMP as a single daily oral dose of 30 mg/kg for the first four days of induction therapy. The number of CD34+ progenitor cells were determined by flow cytometry before and after four days of HDMP treatment. While the number of PB blast cells significantly decreased after only a four-day course of HDMP treatment, the number of PB CD34+ progenitor cells increased in all patients. In addition, after four days of HDMP treatment polymorphonuclear leukocytes (PMN) and mononuclear cells (MNC) increased significantly (p < 0.05). We suggest that the potential beneficial effects of HDMP in the induction treatment of acute leukemia may occur partly by the stimulation of PB CD34+ hematopoietic progenitor cells in a short period of time.
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Abstract A stable poly(crystal-violet) (PCV) electroactive film was electrodeposited on a glassy carbon electrode (GCE). The redoxation of hydroquinone showed a pair of well-defined peaks on a PCV electrode with a potential difference of 30 mV, which is 120 mV less than that obtained on the GCE. At optimal conditions, the PCV electrode linearly responded to the hydroquinone in the range of 4 × 10−6 mol · L−1 to 3.2 × 10−3 mol · L−1 and a detection limit of 8 × 10−8 mol · L−1 was obtained. The separations of the oxidation peak potentials between hydroquinone and the coexisting o-hydroquinone and m-hydroquinonewere 100 mV and 430 mV, respectively, which allows their simultaneous determination. The detection of hydroquinone in artificial sewage water was demonstrated with satisfactory results.
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Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34+ progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects.CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34+ cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34+ cells failed to proof its effect on endothelial cells in vivo.The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34+ progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.
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Objective:To determine the effects of FL,rIL 6,rIL 6R in vitro expansion and differentiation of human cord blood CD34 + cells.Methods:Human cord blood CD34 + cells were enriched by magnetic cell isolation system CD34 + cells were incubated in the presence of FL,rIL 6,rIL 6R and their various companision.The total number of cells and colonies were counted at various time intervals.Results:The expanded cells by FL,rIL 6,rIL 6R showed colonies were CFU GM mainly but rIL 6+rIL 6R and FL+rIL 6+rIL 6R,showed some BFU E and CFU Mix but no CFU MK.Erythrocyte cells were conformed and total cells were increased 6.4 folds by FL+rIL 6+rIL 6R.Conclusion:Human cord blood CD34 + cells could expanded and differentiated by FL+rIL 6+rIL 6R.
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Abstract Background: Despite treatment advances, systemic lupus erythematosus (SLE) patients frequently experience disease flares, which can lead to organ damage and premature death. Therefore, assessing disease activity in SLE patients is crucial for adjusting treatment and preventing further organ damage. The aim of this study was to investigate progenitor cells and circulating endothelial cells levels in relation to SLE activity and accumulate organ damage. Methodos: A case-control study was conducted. CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor, Endothelial Progenitor cells (EPC) and Circulating Endothelial cells (CEC) levels in peripheral blood were assessed by flow cytometry. Results: Thirty-two SLE patients and 28 matched controls were included. SLE patients had lower levels of CD34 + CD45 low/- progenitor cells (p=0.001), CD34 + CD45 low/- CD133 + progenitor cells (p=0.016), EPC (p=0.018) and CEC (p<0.001) compared to controls. In addition, cell subpopulations studied correlate with SLE activity biomarkers. CD34 + CD45 low/- progenitor cells showed a moderate negative correlation with levels of both C3 and C4. We also found significantly higher levels of CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor cells, EPC and CEC in patients with SLE with SDI scores ≥1 versus those without organ damage (p=0.0073, p=0.018, p=0.018 and p=0.020, respectively). Conclusion: We found that CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor cells, CPE and CEC were significantly reduced in patients with SLE as well as associated with disease activity and organ damage. Our observations suggest that CD34 + CD45 low/- progenitor cells could serve as a potential biomarker for disease activity and organ damage in SLE patients. It should be confirmed in a prospective study.
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