Abstract 2482: Bat3 facilitates histone H3 lysine 79 dimethylation by DOT1L to promote ionizing radiation-induced 53BP1 foci formation during G1- and G2-phases of the cell cycle

OBJECT Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. METHODS An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. RESULTS Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. CONCLUSIONS Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Radiation-induced markers/targets may have high discriminating power to be harnessed in vascular targeting for AVM treatment.

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Taurine Protects Mouse Spermatocytes from Ionizing Radiation-Induced Damage Through Activation of Nrf2/HO-1 Signaling

Cellular Physiology and Biochemistry ◽

10.1159/000485762 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1629-1639 ◽

Cited By ~ 12

Author(s):

Wenjun Yang ◽

Jinfeng Huang ◽

Bang Xiao ◽

Yan Liu ◽

Yiqing Zhu ◽

...

Keyword(s):

Cell Cycle ◽

Ionizing Radiation ◽

Cell Viability ◽

Reproductive System ◽

Protective Role ◽

Cell Viability Assay ◽

Drug Candidates ◽

Viability Assay ◽

Taurine Treatment ◽

Radiation Induced

Background/Aims: The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. Methods: mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine. The effect of ionizing radiation and Taurine treatment on GC-2 cells were evaluated by cell viability assay (CCK8), cell cycle and apoptosis. The relative protein abundance change was determined by Western blotting. The siRNA was used to explore whether Nrf2 signaling was involved in the cytoprotection of Taurine. Results: Taurine significantly inhibited the decrease of cell viability, percentage of apoptotic cells and cell cycle arrest induced by ionizing radiation. Western blot analysis showed that taurine significantly limited the ionizing radiation-induced down-regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system pathway. In addition, taurine treatment significantly increased the expression of Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2. Conclusion: Our results demonstrate that taurine has the potential to effectively protect GC-2 cells from ionizing radiation- triggered damage via upregulation of Nrf2/HO-1 signaling.

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Id2Reverses Cell Cycle Arrest Induced by γ-Irradiation in Human HaCaT Keratinocytes

Journal of Biological Chemistry ◽

10.1074/jbc.m414216200 ◽

2005 ◽

Vol 280 (16) ◽

pp. 15836-15841 ◽

Cited By ~ 13

Author(s):

Sandrine Baghdoyan ◽

Jérôme Lamartine ◽

David Castel ◽

Amandine Pitaval ◽

Yoann Roupioz ◽

...

Keyword(s):

Cell Cycle ◽

Ionizing Radiation ◽

Cell Cycle Arrest ◽

Cell Fate ◽

Physiological Role ◽

Human Keratinocytes ◽

Γ Irradiation ◽

Cycle Arrest ◽

Radiation Induced ◽

The Impact

Id2 plays a key role in epithelial cells, regulating differentiation, the cell cycle, and proliferation. Because human skin constantly renews itself and is the first target of irradiation, it is of primary interest to evaluate whether such a gene may be regulated in keratinocytes exposed to ionizing radiation. We show here thatId2is induced in response to γ-irradiation and have investigated the consequence of this regulation on cell fate. Using RNA interference, we observed that Id2 extinction significantly reduces cell growth in human keratinocytes through the control of the G1-S transition of the cell cycle. We have investigated whether the impact of Id2 on the cell cycle may have a physiological role on the cell's ability to cope with radiative stress. Indeed, when Id2 is down-regulated through interfering RNA, cells are more sensitive to irradiation. Conversely, when Id2 is overexpressed, this somehow protects the cell. We propose that Id2 favors reentering the cell cycle after radiation-induced cell cycle arrest to permit the recovery of keratinocytes exposed to ionizing radiation.

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The effect of ATM knockdown on ionizing radiation-induced neuronal cell cycle reentry in Drosophila

Cell Cycle ◽

10.4161/cc.9.13.12185 ◽

2010 ◽

Vol 9 (13) ◽

pp. 2686-2687

Author(s):

Stacey A. Rimkus ◽

Andrew J. Petersen ◽

Rebeccah J. Katzenberger ◽

David A. Wassarman

Keyword(s):

Cell Cycle ◽

Ionizing Radiation ◽

Neuronal Cell ◽

Cell Cycle Reentry ◽

Radiation Induced

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DNA Damage Caused by Ionizing Radiation in Embryonic Diploid Fibroblasts WI-38 Induces Both Apoptosis and Senescence

Physiological Research ◽

10.33549/physiolres.932083 ◽

2011 ◽

pp. 667-677 ◽

Cited By ~ 14

Author(s):

J. CMIELOVÁ ◽

R. HAVELEK ◽

A. JIROUTOVÁ ◽

R. KOHLEROVÁ ◽

M. SEIFRTOVÁ ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Ionizing Radiation ◽

Cellular Response ◽

Diploid Fibroblasts ◽

Cycle Arrest ◽

Permanent Cell ◽

Radiation Induced ◽

G2 Phase ◽

Stress Induced Premature Senescence

Cellular response to ionizing radiation-induced damage depends on the cell type and the ability to repair DNA damage. Some types of cells undergo apoptosis, whereas others induce a permanent cell cycle arrest and do not proliferate. Our study demonstrates two types of response of embryonic diploid fibroblasts WI-38 to ionizing radiation. In the WI-38 cells p53 is activated, protein p21 increases, but the cells are arrested in G2 phase of cell cycle. Some of the cells die by apoptosis, but in remaining viable cells p16 increases, senescence associated DNA-damage foci occur, and senescence-associated beta-galactosidase activity increases, which indicate stress-induced premature senescence.

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The inhibition of p21 on irradiation-induced apoptosis in EL-4 cells.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e13558 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e13558-e13558

Author(s):

Feng-qin Yan ◽

Jian-qiu Wang ◽

Shi-bo Fu ◽

Fang-zheng Wang ◽

Zhen-fu Fu ◽

...

Keyword(s):

Cell Cycle ◽

Ionizing Radiation ◽

Time Course ◽

Apparent Difference ◽

X Rays ◽

X Ray ◽

Radiation Induced ◽

Induced Apoptosis ◽

Diploid Cells

e13558 Background: To elucidate the effect of p21 on ionizing radiation-induced apoptosis in EL-4 cells. Methods: In EL-4 cells, RT-PCR, immunocytochemistry and flow cytometry (FCM) were used to analyze the changes in the expression of p21 with time and doses caused by ionizing radiation; RNAi was used to silence the expression of p21 in EL-4 cells; FCM was applied to analyze the distribution of cell cycle,the number of the chromosome and the apoptosis in wild or p21-silencing EL-4 cells exposed to X-rays. Results: In EL-4 cells, p21 protein level was markedly increased at 8 ~ 72 h after exposure in 4.0 Gy of X-ray in vitro (p<0.01), as well as exposed in 1.0 ~ 4.0 Gy of X-ray at 24 h in vitro (p<0.05). Results of time-course experiments showed that, in EL-4 cells exposed to 4.0 Gy X-rays, the percentage in G0/G1 phase increased while that in S phase decreased, significantly different with the sham-irradiated groups (p<0.05), during 8-48h after exposure; the percentage of diploid cells increased significantly during 8-48 h (p<0.01), and the percentage of tetraploid and octoploid cells decreased significantly at 2 h and 8 h (p<0.05); the percentage of apoptosis during 2-72 h increased significantly (p<0.05-p<0.01). Compared with wild EL-4 cells, in p21-silencing EL-4 cells, the distribution of cell cycle had no apparent difference; the percentage of diploid cells decreased significantly and the percentage of octoploid cells increased significantly (p<0.01); the percentage of apoptosis increased significantly (p<0.05). Conclusions: p21 inhibited the apoptosis induced by ionizing radiation in EL-4 cells.

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