Abstract:
PURPOSE:Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. MATERIALS AND METHODS:The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. RESULTS:The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. CONCLUSIONS:While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue.
journal_name
Int J Radiat Bioljournal_title
International journal of radiation biologyauthors
Bergeron RJ,Wiegand J,Singh Sdoi
10.1080/09553000902781089subject
Has Abstractpub_date
2009-04-01 00:00:00pages
348-61issue
4eissn
0955-3002issn
1362-3095pii
910751539journal_volume
85pub_type
杂志文章abstract:PURPOSE:Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing r...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000110089991
更新日期:2002-01-01 00:00:00
abstract:PURPOSE:To obtain compounds that will effectively reduce the fixation of uranium in its main target organs: bone and kidney. There is an urgent need for a chelating agent that is suitable and available for human use. MATERIALS AND METHODS:The efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP), already in use as a ...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/095530099139331
更新日期:1999-11-01 00:00:00
abstract:PURPOSE:Biomarkers of ionising radiation exposure are useful in a variety of scenarios, such as medical diagnostic imaging, occupational exposures, and spaceflight. This study investigates to what extent microRNA (miRNA) expression signatures in mouse peripheral blood can be used as biomarkers for exposures to radiatio...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2010.549537
更新日期:2011-07-01 00:00:00
abstract:PURPOSE:Multicellular tumour spheroids are being used with increasing frequency in various aspects of tumour biology, including studies dealing with radiation biology. This review attempts to outline recent studies using these three-dimensional systems in radiation biology with particular reference made to papers testi...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/095530099139845
更新日期:1999-07-01 00:00:00
abstract::Purpose: Dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. The results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553002.2019.1625462
更新日期:2019-09-01 00:00:00
abstract:PURPOSE:To investigate cell cycle effects and relative biological effectiveness (RBE) of α-particles from the clinically relevant radionuclide Astatine-211 ((211)At), using X-rays as reference radiation. Double-strand breaks (DSB), non-DSB clusters containing oxidised purines and clonogenic survival were investigated. ...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2011.538127
更新日期:2011-04-01 00:00:00
abstract::Determinations of cell sensitivity in terms of survival fraction after doses employed in clinical radiation therapy, say 1-3 Gy, are of increasing interest to clinicians as they provide direct experimental data which can be employed without reference to models of cell inactivation. SF2 values are expected ultimately t...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553008914551971
更新日期:1989-11-01 00:00:00
abstract::Murine bone marrow contains osteogenic precursor cells that undergo differentiation during in vitro cultivation. In vitro these cells are potential target cells for alpha-irradiation-induced bone tumour formation. Under defined tissue culture conditions these differentiating cells were directly exposed to alpha-partic...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009414551111
更新日期:1994-08-01 00:00:00
abstract:PURPOSE:Recently, it was found that MK615 possessed an anti-proliferative ability on treated cancer cells as a consequence of triterpenoid compounds. It is well known that radiation affects cellular-mediated immunity in cancer patients who are treated with radiotherapy. Similarly, the ability of triterpenoid compounds ...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2010.518202
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:This review is a contribution to the memory of Dr William (Bill) Morgan and highlights an area of research and deliberation that he considered extremely important in support of the setting of protective radiation dose limits. Biological research has generally played a minor role in the estimation of adverse hea...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553002.2017.1290848
更新日期:2017-10-01 00:00:00
abstract:PURPOSE:Many studies have shown that exposure to radiofrequency radiation (RFR) could activate cellular signal transduction pathways. In the present research, we investigated the effects of exposure to a 1.8-GHz RFR at different intensities on epidermal growth factor (EGF) receptor clustering and phosphorylation in hum...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2011.634882
更新日期:2012-03-01 00:00:00
abstract::The relative contributions of the OH-mediated and direct radiation effect on the induction of DNA double-strand breaks (dsbs) were evaluated in two haploid yeast cell lines (GSH+ and gsh-) irradiated under oxic or hypoxic conditions in the absence or presence of 6 M glycerol as an OH radical scavenger. Gsh- cells are ...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009314551721
更新日期:1993-11-01 00:00:00
abstract:PURPOSE:To investigate within the framework of a multilaboratory study the suitability of FISH chromosome painting to measure so-called stable translocations in peripheral lymphocytes of Mayak nuclear-industrial workers (from the Southern Urals) and their use for retrospective biodosimetry. MATERIALS AND METHODS:Chrom...
journal_title:International journal of radiation biology
pub_type: 杂志文章,多中心研究
doi:10.1080/09553000010018693
更新日期:2001-03-01 00:00:00
abstract::Cells use substrates such as glucose and glutamine to provide energy for repair of radiation damage. Glutaminolysis and glycolysis were inhibited by aminooxyacetic acid (AOAA) and 2-deoxyglucose (2DG), respectively, to inhibit metabolism of these substrates in order to determine the effect on radiation response of CHO...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/095530098142419
更新日期:1998-03-01 00:00:00
abstract::Purpose: Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (NIRS), have focused on risk analyses for life shortening and cancer prevalence using laboratory animals. Genetic and epigenetic al...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553002.2019.1625458
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2013.762136
更新日期:2013-05-01 00:00:00
abstract:PURPOSE:Conditionally Replicative Adenovirus (CRAd) has been previously demonstrated to augment the activity of radiation, resulting in synergy of cell kill. However, previous models combining radiation with CRAd have not focused on the methods of radiation delivery. MATERIALS AND METHODS:We model the combination of a...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553000903419338
更新日期:2010-03-01 00:00:00
abstract:PURPOSE:Many strategies have been investigated to exclude the several side-effects of pharmacological or invasive treatments. Non-invasive pulsed magnetic field (PMF) treatment with no toxicity or side-effects can be an alternative to pharmacologic treatments. The purpose of this study was, therefore, to investigate th...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2013.835501
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:To analyze the direct and transgenerational effects of exposure to low-dose 1 GHz (mobile phone/wireless telecommunication range) and 10 GHz (radar/satellite communication range) radiofrequency electromagnetic fields (RF-EMF) on the motility of ciliates Spirostomum ambiguum. MATERIALS AND METHODS:S. ambiguum w...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2014.868612
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:The deleterious processes triggered by heavy ions on DNA were studied through the determination of the yield of a series of oxidized bases. Emphasis was placed on the estimation of the respective contribution of direct ionization and indirect effects, mostly by comparison with low linear energy transfer (LET) g...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000600573788
更新日期:2006-02-01 00:00:00
abstract::A radionuclide release assay for measuring the in vitro kinetics of cell death has been developed. CHO cells were labelled for 24 h with 3.0 hBq/ml of [125I] iododeoxyuridine (125IUdR) and the fate of the labelled cells and their progeny was monitored at daily intervals by measuring the rate of 125I release. Prelabell...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009114550361
更新日期:1991-02-01 00:00:00
abstract:PURPOSE:Therapy with low doses of ionising radiation (X-rays) exerts anti-inflammatory effects. Little is known about whether and how low doses of X-ray treatment modulate the inflammatory phenotype of macrophages, especially the secretion of Interleukin-1beta (IL-1β). MATERIALS AND METHODS:Macrophages were differenti...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2012.689464
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553002.2017.1231942
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long-term genome damage in patients with seminoma after radiotherapy. MATERIALS AND MET...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2013.825057
更新日期:2013-11-01 00:00:00
abstract::Eelpout (Zoarces viviparus), a marine fish, were exposed to gamma-radiation at a dose-rate of 2.0 mGy h-1. They were injected with the antigen trinitrophenyl-keyhole limpet haemocyanin (TNP-KLH) and their specific humoral immune response to the TNP hapten measured. There were no differences in the primary antibody res...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009514550091
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors. MATERIALS AND METHODS:Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ra...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553002.2017.1400192
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:In case of a large-scale radiation accident when hundreds of people may be exposed, it is important to distinguish the severely exposed individuals (> or =1 gray), who require early medical treatment, from those less exposed. The aim of our study was to develop a quick population triage method based on automate...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553000903264481
更新日期:2010-01-01 00:00:00
abstract::The aim was to review and summarize the results of 40 years of study concerning the response to ionizing radiation of the pair of L5178Y (LY) sublines, LY-R and LY-S, that differ in sensitivity to various DNA-damaging agents, among them X- and gamma-rays. The reviewed data indicate the key importance of DNA damage rep...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553000500143534
更新日期:2005-05-01 00:00:00
abstract:PURPOSE:We computed probabilities to have multiple double-strand breaks (DSB), which are produced in DNA on a regional scale, and not in close vicinity, in volumes matching the size of DNA damage foci, of a large chromatin loop, and in the physical volume of DNA containing the HPRT (human hypoxanthine phosphoribosyltra...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000802499212
更新日期:2008-11-01 00:00:00
abstract:PURPOSE:To investigate the ability of electromagnetic (EM) field pre-exposures to induce protection in chick embryos against subsequent ultraviolet (UV) light exposure. MATERIALS AND METHOD:Chick embryos in the 4th day of gestation were exposed for 20 minutes (short term) or 96 hours (long term) to 60 Hz, 8 microT mag...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/095530099139142
更新日期:1999-12-01 00:00:00