Abstract:
:Tumor radiotherapy with large-field irradiation results in an increase of p53-dependent apoptosis of the radiosensitive hematopoietic stem cells. Proapoptotic PUMA is a transcriptional target of p53. Thus suppression of PUMA expression by gene therapy with the transcription repressor SNAI2 as transgene might be a potential approach for normal tissue protection during radiotherapy. SNAI2 cDNA was cloned in a lentiviral SIN vector in a bicistronic expression cassette followed by a floxed IRES-EMCV linker and EGFP as selection gene. Wild-type p53 TK6 cells were used as the cellular model system. We could demonstrate the significant radioprotective effect of SNAI2 overexpression in a cytotoxicity assay after irradiation with 0-5 Gy compared with untransduced or control vector (inverse oriented SNAI2 cDNA)-transduced cells. Additionally, TK6-SNAI2 compared to TK6-SNAI2inv cells showed a survival advantage in a clonogenic assay after irradiation with 0-3 Gy. Determination of the proportion of sub-G(1) cells in TK6-SNAI2 cells revealed an approximately 50% reduction in apoptosis compared with both control entities. In this study using a bicistronic lentiviral vector, we were able to provide proof of principle that lentiviral overexpression of SNAI2 might be used for radioprotective gene therapy to widen the therapeutic range in radiotherapy.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Maier P,Herskind C,Barzan D,Zeller WJ,Wenz Fdoi
10.1667/RR1952.1subject
Has Abstractpub_date
2010-05-01 00:00:00pages
612-9issue
5eissn
0033-7587issn
1938-5404journal_volume
173pub_type
杂志文章abstract::Chinese hamster ovary (CHO) cells were exposed to various concentrations of diethylmaleate (DEM) during a 42 degrees C incubation to determine if glutathione (GSH) compartmentalization was a factor in modification of thermal sensitivity. Cytoplasmic and mitochondrial GSH were isolated from CHO cells immediately after ...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::The placental transfer and distribution of 241Am in the feto-placental system were studied in pregnant rats. Rats were injected intravenously with 241Am citrate at 15 or 18 days of gestation. Groups injected at 15 days of gestation were sacrificed 2, 24, 48, or 120 hr after injection, and the group injected at 18 days...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract::A recently developed method for the direct measurement of the restricted dose mean LET (cutoff energy = 500 eV) of an unspecified photon or electron radiation field with the high-pressure ionization chamber has been utilized to investigate the variation of this radiobiologically important parameter outside the primary...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2007)168[183:HGUCTW]2.0.CO;2
更新日期:2007-08-01 00:00:00
abstract::The effects of (56)Fe particles and (137)Cs gamma radiation were compared in TK6 and WTK1 human lymphoblasts, two related cell lines which differ in TP53 status and in the ability to rejoin DNA double-strand breaks. Both cell lines were more sensitive to the cytotoxic and clastogenic effects of (56)Fe particles than t...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2001)156[0186:geohei]2.0.co;2
更新日期:2001-08-01 00:00:00
abstract::Evaluating the risk for central nervous system (CNS) effects after whole-body or partial-body irradiation presents challenges due in part to the varied exposure scenarios in the context of occupational, accidental or wartime releases. Risk estimations are further complicated by the fact that robust changes in brain fu...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR15413.1
更新日期:2020-01-01 00:00:00
abstract::Plateau-phase A549 cells exhibit a high capacity for repair of potentially lethal radiation damage (PLD). Previously it was found that PLD repair could be partially inhibited by increasing the extracellular pH (pHe) of the spent medium from its normal value of 6.7-6.8 to 7.6 during postirradiation holding. The present...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::Cataract is one of the major morbidities in the U.S. population and it has long been appreciated that high and acutely delivered radiation doses of 1 Gy or more can induce cataract. Some more recent studies, in particular those of the U.S. Radiologic Technologists, have suggested that cataract may be induced by much l...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR15529.1
更新日期:2020-08-01 00:00:00
abstract::After DNA damage, caspases cleave and activate proteins involved in cell death by apoptosis but also cleave and inactivate proteins implicated in DNA repair. Here we report a rapid onset of Rad51 cleavage by caspase 3 in BRCA2-defective mouse and human cells. This rapid cleavage was reduced markedly by transfer of ful...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR1129.1
更新日期:2008-05-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章,评审
doi:10.1667/RR15553.1
更新日期:2020-03-01 00:00:00
abstract::Molecular oxygen has long been recognized as a powerful radiosensitizer that enhances the cell-killing efficiency of ionizing radiation. Radiosensitization by oxygen occurs at very low concentrations with the half-maximum radiosensitization at approximately 3 mmHg. However, robust hypoxia-induced signal transduction c...
journal_title:Radiation research
pub_type: 杂志文章,评审
doi:10.1667/RR13959.1
更新日期:2015-05-01 00:00:00
abstract::The molecular structure of mutants induced in human lymphoblast cells by 500 cGy X rays in the presence of the radioprotector cysteamine (25 mM) has been compared with that induced by an equally mutagenic treatment of 150 cGy X rays alone. Sets of mutants at the hypoxanthine-guanine phosphoribosyl transferase locus we...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Technological developments in radiation therapy and other cancer therapies have led to a progressive increase in five-year survival rates over the last few decades. Although acute effects have been largely minimized by both technical advances and medical interventions, late effects remain a concern. Indeed, the need t...
journal_title:Radiation research
pub_type: 杂志文章,评审
doi:10.1667/rr2530.1
更新日期:2012-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR15566.1
更新日期:2020-07-08 00:00:00
abstract::Relationships based on the microdosimetric-kinetic model are presented that calculate the average number of lethal lesions, and the associated cell survival, produced in mammalian cells by exposure to protracted continuous irradiation by temporary and permanent implantation of radioactive sources. The influence of cel...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR13558.1
更新日期:2014-07-01 00:00:00
abstract::The Escherichia coli nth gene encodes endonuclease III, which catalyses the glycolytic removal of various oxidized thymine residues from DNA. A truncated version of nth, with the prokaryotic regulatory sequences removed, was ligated into the retrovirus-based vector pZipneoSV(X)1 and transfected into the radiosensitive...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Hemodynamic shear stress is defined as the physical force exerted by the continuous flow of blood in the vascular system. Endothelial cells, which line the inner layer of blood vessels, sense this physiological force through mechanotransduction signaling and adapt to maintain structural and functional homeostasis. Hem...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR14410.1
更新日期:2016-08-01 00:00:00
abstract::It has been acknowledged for many years that radiation exposure induces delayed, non-targeted effects in the progeny of the irradiated cell. Evidence is beginning to demonstrate that among these delayed effects of radiation are epigenetic aberrations, including altered DNA methylation. To test the hypothesis that diff...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR2390.1
更新日期:2011-05-01 00:00:00
abstract::Monte Carlo simulations are used in the development of a nanotechnology-based multi-pixel beam array small animal microirradiation system. The microirradiation system uses carbon nanotube field emission technology to generate arrays of individually controllable X-ray pixel beams that electronically form irregular irra...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR1453.1
更新日期:2009-03-01 00:00:00
abstract::Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung can...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR0848.1
更新日期:2008-02-01 00:00:00
abstract::Mortality data for B6CF1 mice exposed to 60Co gamma rays for the duration of life were used to make quantitative predictions of age-specific mortality observed in comparably exposed beagles. Simple Kaplan-Meier survival curves for the beagles and their 95% confidence intervals were computed for each dose-rate group ob...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::These assessment of the consequences of irradiation on chromatin is complicated by endogenous nucleases. Isolation and prolonged storage of rat liver nuclei in buffers containing divalent metal ions activates these enzymes and promotes the degradation of chromatin. Irradiation of rat liver nuclei to dose levels of 20,...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR2927.1
更新日期:2013-02-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothe...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Human keratinocytes show a bystander effect when exposed to low doses of low-LET radiation. In this paper, data are presented showing a method of correcting the overall survival curve to enable analysis of the relative contributions of the bystander effect and the effect attributable to direct interaction of the radia...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2000)153[0508:rcobat]2.0.co;2
更新日期:2000-05-01 00:00:00
abstract::The effects of 2.45-GHz continuous-wave microwaves (SAR = 130 mW/g) on the expression of the interferon-regulated enzymes 2'-5'-oligoadenylate (2-5A) synthetase(s) and 2-5A-dependent endoribonuclease (RNase L) were studied in murine L929 cells. Cells growing as monolayers were removed from the substratum and placed in...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::To compare the genotoxic effects of high-LET ionizing radiation to those of low-LET radiation, we investigated the responses of human lymphoblastoid cells to DNA damage TK6 after treatment with either low-LET X rays or high-LET iron ions (1000 keV/microm). A highly localized distribution of gammaH2AX/RAD51 foci was ob...
journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2002)158[0678:dccpih]2.0.co;2
更新日期:2002-12-01 00:00:00
abstract::Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy ...
journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation R...
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pub_type: 杂志文章
doi:10.1667/rr3096
更新日期:2003-12-01 00:00:00