Abstract：
:Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (≥24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage. Using γ-H2AX as a measurement of DNA damage in MCF-7 breast cancer cells, we demonstrate that 10 or 80 nM dFdCyd alone produced significantly more late DNA damage compared to that observed within 4 h after treatment. The combination of dFdCyd treatment followed by irradiation did not produce a consistent increase in DNA damage in the first 4 h after treatment, however, there was a synergistic increase 24-48 h later relative to treatment with dFdCyd or radiation alone. RNAi suppression of the essential HRR protein, XRCC3, significantly decreased both radiosensitization and late DNA damage. Furthermore, inhibition of HRR with the Rad51 inhibitor B02 prevented radiosensitization when added after, but not during, treatment with dFdCyd and radiation. To our knowledge, this is the first published study to show that radiosensitization with dFdCyd results from a synergistic increase in DNA damage at 24-48 h after drug and radiation treatment, and that this damage and radiosensitization require HRR. These results suggest that tumors that overexpress HRR will be more vulnerable to chemoradiotherapy, and treatments that increase HRR and/or mismatches in DNA will enhance dFdCyd radiosensitization.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Im MM,Flanagan SA,Ackroyd JJ,Knapp B,Kramer A,Shewach DSdoi
10.1667/RR14443.1subject
Has Abstractpub_date
2016-11-01 00:00:00pages
466-477issue
5eissn
0033-7587issn
1938-5404journal_volume
186pub_type
杂志文章abstract：:The purpose of this paper is to validate a metabolic model describing the kinetics of tritium in man. The validation is based on measurements of background levels of loose and bound tritium in Italian subjects and their diets. Model predictions are compared with empirical measurements of tritium in human urine and tis...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-12-01 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：:This study was designed to determine whether patients taking angiotensin-converting enzyme (ACE) inhibitors while receiving radiation therapy for lung cancer are protected from developing symptomatic radiation pneumonitis. The records of 213 eligible patients receiving thoracic irradiation for lung cancer with curativ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2000)153[0405:caceip]2.0.co;2
更新日期：2000-04-01 00:00:00
abstract：:To compare the effects of exposure to a near-resonant frequency of microwaves at two orientations with a higher frequency exposure, five rhesus monkeys were exposed for 4 hr to 225 MHz, electric field oriented parallel to the long axis of the body (225 MHz-E), and to 225 MHz, magnetic field orientation (225 MHz-H), or...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1414.1
更新日期：2008-12-01 00:00:00
abstract：:We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such a...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3360
更新日期：2005-05-01 00:00:00
abstract：:Ionizing radiation induces bistranded clustered damages--two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although i...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3498.1
更新日期：2006-02-01 00:00:00
abstract：:Statistical analysis of Monte Carlo simulations of positive ion track structure is presented for 1 MeV protons passing outside an absorbing region of interest. Energy deposition and production of ionization within the region occur only by delta-ray transport from the ion's path. Depositions in spherical absorber regio...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:A biphasic curve was observed when surviving allogeneic lytic activity was plotted as a function of irradiation delivered before sensitization. Flow cytometry analysis demonstrated that the number of cells was reduced in response to increasing dose and that subset precursors Lyt 1+2+ were proportionally more radiosens...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Therapeutic gain factors (TGFs) have been determined for three spontaneous tumors of the C3H mouse treated by photons + normobaric oxygen (O2(1) ATA), photons + hyperbaric oxygen (O2 3 ATA), photons + misonidazole, or fast neutrons. The tumors were early generation isotransplants of spontaneous tumors: MCaIV, a mammar...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:This report compares the deterministic effects from an alpha-particle-emitting radionuclide, (239)PuO(2), and a beta-particle emitter, (144)Ce in fused aluminosilicate particles (FAP). The studies were conducted in beagle dogs of both genders exposed by inhalation to aerosols of the radionuclides. The initial lung bur...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:A historical cohort mortality study was conducted among 28,008 white male employees who had worked for at least 1 month in Oak Ridge, Tennessee, during World War II. The workers were employed at two plants that were producing enriched uranium and a research and development laboratory. Vital status was ascertained thro...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:There are public concerns regarding possible carcinogenic or cancer-promoting effects of electromagnetic fields (EMFs) from mobile phones and base stations. The objective of the present study was to investigate whether chronic exposure to EMFs of the UMTS (Universal Mobile Telecommunication System) influences the deve...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR0857.1
更新日期：2007-07-01 00:00:00
abstract：:To determine whether different agents that enhance the expression of potentially lethal X-ray damage (PLD) interact with the same or different lesions (or spectrum of lesions), cell killing was measured in three kinds of experiments: (1) When cells were irradiated in G1 phase and treated with caffeine or hydroxyurea a...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Pulse radiolysis and 60Co gamma radiolysis were used to study the effects of ionizing radiations on the activity of glutamate dehydrogenase. Hydroxyl radicals are considerably more effective than hydrated electrons in causing loss of enzymatic activity. Evidence is also presented that the free radical anions (SCN)-.2,...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:The effect of age at exposure on induction of mammary carcinoma was studied in female rats of the inbred WAG/Rij strain that were treated with estrogen. Groups of 40 animals were exposed to a single total-body dose of 1 or 2 Gy of 137Cs gamma radiation at age 8, 10, 12, 15, 22, 36 or 64 weeks. Hormone levels in the an...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:The microdosimetry of (10)B thermal neutron capture reactions should be considered as an essential step to be followed before studying the radiobiological aspects of boron neutron capture therapy. The boron dose itself is insufficient as the only quantity used to describe the biological effectiveness of the (10)B reac...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3257
更新日期：2004-12-01 00:00:00
abstract：:Experimental work indicates that one of the mechanisms of tumor control by hyperthermia may be damage to blood vessels, resulting in decreased blood flow to the neoplasms. Among the various elements of the microvasculature, endothelial cells are the most important possible targets of thermal injury. Furthermore, neopl...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:Cells from patients with ataxia telangiectasia (AT) are abnormal in their response to irradiation as judged by clonogenic survival and accumulation in G2 phase. The relationship of the results of these two assays, however, is still a matter of controversy. Flow cytometry was used to measure the distribution of cells i...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Radiation of the esophagus of C3H/HeNsd mice with 35 or 37 Gy of 6 MV X rays induces significantly increased RNA transcription for interleukin 1 (Il1), tumor necrosis factor alpha (Tnf), interferon gamma inducing factor (Ifngr), and interferon gamma (Ifng). These elevations are associated with DNA damage that is detec...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)155[0002:morice]2.0.co;2
更新日期：2001-01-01 00:00:00
abstract：:Using atomic force microscopy (AFM), we have investigated neutron-induced DNA double-strand breaks in plasmids in aqueous solution. AFM permits direct measurement of individual DNA molecules with an accuracy of a few nanometers. Furthermore, the analysis of the DNA fragment size distribution is non-parametric, whereas...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:Human erythrocytes were isolated from the blood of healthy donors and then incubated in the presence of suspensions of alpha-tocopherol for 30 min at 37 degrees C. Unabsorbed tocopherol was removed by centrifugation using several washes of isotonic phosphate-buffered saline. Washed erythrocytes were resuspended to 0.0...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
abstract：:At the outset of the accident at Fukushima Daiichi Nuclear Power Plant in March 2011, the radiation doses experienced by residents were calculated from the readings at monitoring posts, with several assumptions being made from the point of view of protection and safety. However, health effects should also be estimated...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR13351.1
更新日期：2013-11-01 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：:Blockers of the renin-angiotensin-aldosterone system (RAAS) ameliorate cognitive deficits and some aspects of brain injury after whole-brain irradiation. We investigated whether treatment with the angiotensin II type 1 receptor antagonist L-158,809 at a dose that protects cognitive function after fractionated whole-br...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr2560.1
更新日期：2011-07-01 00:00:00
abstract：:Human immortalized keratinocytes were exposed to a range of single or fractionated doses of gamma rays from (60)Co, to medium harvested from donor cells exposed to these protocols, or to a combination of radiation and irradiated cell conditioned medium (ICCM). The surviving fractions after direct irradiation or exposu...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2002)158[0626:badeaf]2.0.co;2
更新日期：2002-11-01 00:00:00
abstract：:Pulmonary carcinomas were recorded in a life-span experiment of male Sprague-Dawley rats exposed to fission neutrons. Mortality-corrected prevalences are obtained by the method of isotonic regression. In a second part of the paper a comparison is made with data obtained earlier for radon-daughter inhalations in the sa...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-06-01 00:00:00
abstract：:Triple negative breast cancer (TNBC) is an aggressive disease with a high risk of recurrence and death. Here, we present a novel strategy to enhance the radiotherapy of TNBC by combining gold nanoparticles (AuNPs) with pentamidine, a clinically approved anti-parasitic agent with anti-cancer properties. The radiosensit...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR14315.1
更新日期：2016-05-01 00:00:00
abstract：:The primary risk factors of multiple myeloma are age, race and sex, but several studies have found an association between radiological hazards and multiple myeloma. The purpose of this nested case-control study was to investigate whether workers with chronic low-level exposure to internally deposited uranium at the Oa...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1607.1
更新日期：2009-06-01 00:00:00
abstract：:Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by 60Co gamma rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized auto...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
