Microwaves from mobile phone induce reactive oxygen species but not DNA damage, preleukemic fusion genes and apoptosis in hematopoietic stem/progenitor cells

Abstract Exposure to electromagnetic fields (EMF) has been associated with the increased risk of childhood leukemia, which arises from mutations induced within hematopoietic stem cells often through preleukemic fusion genes (PFG). In this study we investigated whether exposure to microwaves (MW) emitted by mobile phones could induce various biochemical markers of cellular damage including reactive oxygen species (ROS), DNA single and double strand breaks, PFG, and apoptosis in umbilical cord blood (UCB) cells including CD34+ hematopoietic stem/progenitor cells. UCB cells were exposed to MW pulsed signals from GSM900/UMTS test-mobile phone and ROS, apoptosis, DNA damage, and PFG were analyzed using flow cytometry, automated fluorescent microscopy, imaging flow cytometry, comet assay, and RT-qPCR. In general, no persisting difference in DNA damage, PFG and apoptosis between exposed and sham-exposed samples was detected. However, we found increased ROS level after 1 h of UMTS exposure that was not evident 3 h post-exposure. We also found that the level of ROS rise with the higher degree of cellular differentiation. Our data show that UCB cells exposed to pulsed MW developed transient increase in ROS that did not result in sustained DNA damage and apoptosis.

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Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia

Journal of Visualized Experiments ◽

10.3791/59593 ◽

2019 ◽

Author(s):

Daniela Di Marcantonio ◽

Stephen M. Sykes

Keyword(s):

Reactive Oxygen Species ◽

Progenitor Cells ◽

Flow Cytometric Analysis ◽

Reactive Oxygen ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Hematopoietic Stem ◽

Flow Cytometric ◽

Stem And Progenitor Cells

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FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulation

Blood ◽

10.1182/blood-2011-11-394692 ◽

2012 ◽

Vol 120 (9) ◽

pp. 1843-1855 ◽

Cited By ~ 66

Author(s):

Tomer Itkin ◽

Aya Ludin ◽

Ben Gradus ◽

Shiri Gur-Cohen ◽

Alexander Kalinkovich ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Progenitor Cells ◽

Stromal Cells ◽

Reactive Oxygen ◽

Receptor Activation ◽

Oxygen Species ◽

Hematopoietic Stem ◽

Cell Engraftment ◽

Stem And Progenitor Cells

Abstract Cytokine-induced expansion of hematopoietic stem and progenitor cells (HSPCs) is not fully understood. In the present study, we show that whereas steady-state hematopoiesis is normal in basic fibroblast growth factor (FGF-2)–knockout mice, parathyroid hormone stimulation and myeloablative treatments failed to induce normal HSPC proliferation and recovery. In vivo FGF-2 treatment expanded stromal cells, including perivascular Nestin+ supportive stromal cells, which may facilitate HSPC expansion by increasing SCF and reducing CXCL12 via mir-31 up-regulation. FGF-2 predominantly expanded a heterogeneous population of undifferentiated HSPCs, preserving and increasing durable short- and long-term repopulation potential. Mechanistically, these effects were mediated by c-Kit receptor activation, STAT5 phosphorylation, and reduction of reactive oxygen species levels. Mice harboring defective c-Kit signaling exhibited abrogated HSPC expansion in response to FGF-2 treatment, which was accompanied by elevated reactive oxygen species levels. The results of the present study reveal a novel mechanism underlying FGF-2–mediated in vivo expansion of both HSPCs and their supportive stromal cells, which may be used to improve stem cell engraftment after clinical transplantation.

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Anticancer, Antioxidant Activities and Molecular Docking Study of Thiazolidine -4-one and Thiadiazol Derivatives

10.21203/rs.3.rs-1200559/v1 ◽

2022 ◽

Author(s):

Tahseen Abdul qader Alsalim ◽

Noor M. Nasir ◽

Amr Ahmed El-Arabey ◽

Mohnad Abdalla

Keyword(s):

Reactive Oxygen Species ◽

Flow Cytometry ◽

Antioxidant Activity ◽

Molecular Docking ◽

Liver Cancer ◽

Hepg2 Cells ◽

Reactive Oxygen ◽

Binding Energies ◽

Oxygen Species ◽

Hematopoietic Stem

Abstract Liver cancer accounts for a major portion of the global cancer burden. In many nations, the prevalence of this condition has risen in recent decades. New series of thaiazolidinones and thaiadiazolidine have been designed, synthesized, and evaluated for potential antioxidant and antihepatocarcinogenic activity. The antioxidant activity of synthesized compounds was evaluated using a DPPH assay. Furthermore, we examined the compounds against HepG2 cells using MTT assay, flow cytometry analysis through the cell cycle, reactive oxygen species, and apoptosis. The result showed that compound 6b has the highest antioxidant activity with IC50 =60.614±0.739 µM. The anticancer activity showed that compounds 5 and 6b have significant toxicity against liver cancer cells HepG2, IC50 values (9.082 and 4.712) µM, respectively. Flow cytometry experiments revealed that compound 5 arrested HepG2 cells in the S process, while compound 6b arrested HepG2 cells in the G1. Compound 6b had a greater reduction in reactive oxygen species and late apoptosis than compound 5. Substantially, compound 5 had affinity energies of -7.6 and -8.5 for Akt and CDK4 proteins, respectively, but compound 6b had affinity energies of -7.8 and -10.1 for Akt1 and CDK4 proteins, respectively. Consequently, compound 6b had lower binding energies than compound 5. In this work, we used multiple bioinformatics methods to shed light on the prospective therapeutic use of these series as novel candidates to target immune cells in the tumor microenvironment of hepatocellular carcinomas such as CD8+ T cells, endothelial cells, and hematopoietic stem cells. The results of antioxidant, anticancer, molecular docking studies, and bioinformatic analysis showed that compound 6b has a potential impact and could be developed for drug discovery with further research.

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Loss of Foxo3a In FA Mice Leads to Hematopoietic Stem Cell Exhaustion That Can Be Attenuated by Natural Anti-Oxidant Quercetin.

Blood ◽

10.1182/blood.v116.21.1166.1166 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1166-1166

Author(s):

Jie Li ◽

Jared Sipple ◽

Qishen Pang

Keyword(s):

Reactive Oxygen Species ◽

Progenitor Cells ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Genetic Disorder ◽

Specific Interaction ◽

Reactive Oxygen ◽

Oxygen Species ◽

Hematopoietic Stem ◽

Anti Oxidant

Abstract Abstract 1166 Fanconi anemia (FA) is a genetic disorder characterized by genomic instability, bone marrow (BM) failure and predisposition to cancer. However, FA mouse models do not show spontaneous genetic instability. Previous study shows that FOXO3a is associated with the FA pathway through oxidative stress-specific interaction with FANCD2. To address the consequence of loss of FOXO3a function in FA hematopoiesis, we generated Foxo3a-/-Fancd2-/- and Foxo3a-/-Fancc-/- double-knockout (DKO) mice by crossing Foxo3a+/− with Fancd2+/− or Fancc+/−; mice. Reactive oxygen species are increased in low-density BM (LDBM) cells isolated from DKO mice compared to those from single KO (SKO) or wt mice. Analysis of hematologic parameters shows significantly increased number of nucleate cells and high ratio of eosinophils in peripheral blood of DKO mice. CFU assay shows more progenitor cells in peripheral blood isolated from DKO mice. Moreover, BM progenitor cells from DKO mice exhibit lower adhesion but higher migration activity, compared to those from wt or SKO mice. Consistent with this, Cdc42 pull-down assay shows lower Cdc42 activity in DKO LDBM cells than in wt or SKO cells, indicating that decreased Cdc42 may contribute to the observed aberrant adhesion and migration activities. DKO mice show significant decrease in primitive progenitor (Lin-Sca-1+c-kit+; LSK) cells, increase in BrdU+ and G1-phase LSK cells, and impaired repopulating capacity after competitive BM transplantation, which can be attenuated by the anti-oxidant Quercetin. Taken together, loss of Foxo3a in FA mice results in FA-like syndrome, which may be resulted from increased reactive oxygen species accumulation. Disclosures: No relevant conflicts of interest to declare.

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The Role ofHibiscus sabdariffaL. (Roselle) in Maintenance ofEx VivoMurine Bone Marrow-Derived Hematopoietic Stem Cells

The Scientific World JOURNAL ◽

10.1155/2014/258192 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Zariyantey Abdul Hamid ◽

Winnie Hii Lin Lin ◽

Basma Jibril Abdalla ◽

Ong Bee Yuen ◽

Elda Surhaida Latif ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Stem Cells ◽

Bone Marrow ◽

Dna Damage ◽

Ex Vivo ◽

Reactive Oxygen ◽

Oxygen Species ◽

Sod Activity ◽

Hematopoietic Stem ◽

Murine Bone Marrow

Hematopoietic stem cells- (HSCs-) based therapy requiresex vivoexpansion of HSCs prior to therapeutic use. However,ex vivoculture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role ofHibiscus sabdariffaL. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0–1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival(P<0.05)of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1+cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased(P<0.05)the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.

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