Increased mutability and decreased repairability of a three-lesion clustered DNA-damaged site comprised of an AP site and bi-stranded 8-oxoG lesions.


PURPOSE:Ionizing radiation induces DNA damage, some of which are present in clusters, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. These clusters are thought to contribute to the detrimental effects of radiation, in part due to the compromised repair of clustered DNA damaged sites. MATERIALS AND METHODS:The repair of three-lesion cluster present in oligonucleotides were determined in vitro using the hamster cell line CHO-K1 nuclear extract or purified proteins involved in base excision repair. The mutagenic potential of these clusters present in a plasmid was determined using an Escherichia coli reporter assay. RESULTS:We have shown that the repair of an abasic (AP) site within a three-lesion cluster, comprised of an AP site and bi-stranded 8-oxo-7,8-dihydroguanine (8-oxoG) lesions, is retarded compared to that of an isolated AP site in an in vitro base excision repair (BER) assay. Further, the mutation frequency of the clustered damaged site is up to three times greater than that of an isolated 8-oxoG lesion. CONCLUSIONS:As a consequence of enhanced mutagenic potential of clusters, non-double-strand break (DSB) DNA damage may contribute to the detrimental effects of radiation, in addition to the effects of DSB.


Int J Radiat Biol


Cunniffe S,Walker A,Stabler R,O'Neill P,Lomax ME




Has Abstract


2014-06-01 00:00:00












  • DNA strand scission and base release photosensitized by metallo-phthalocyanines.

    abstract::Photoirradiation of aqueous solutions of DNA in the presence of Al- or Zn-tetrasulphonated phthalocyanines (AIPcS4 and ZnPcS4) causes formation of strand breaks and liberation of nucleobases. The effect of added D2O, which enhances singlet oxygen (1O2) lifetime, radical scavengers including alcohols and the spin-trap ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Gantchev TG,Gowans BJ,Hunting DJ,Wagner JR,van Lier JE

    更新日期:1994-12-01 00:00:00

  • Does tirapazamine (SR-4233) have any cytotoxic or sensitizing effect on three human tumour cell lines at clinically relevant partial oxygen pressure?

    abstract::Solid human tumours contain areas with low oxygen tension (pO2). For bioreductive drugs it is important to define the cytotoxic effect according to drug concentration and to clinically relevant pO2. In this study, the pO2 dependence of the survival of three human cell lines (HRT 18, Na11 +, and MEWO), exposed to tirap...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Lartigau E,Guichard M

    更新日期:1995-02-01 00:00:00

  • Reactions of 5-methylcytosine cation radicals in DNA and model systems: thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar.

    abstract:PURPOSE:To study the formation and subsequent reactions of the 5-methyl-2'-deoxycytidine cation radical (5-Me-2'-dC•(+)) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine. MATERIALS AND METHODS:Employing electron spin resonance (ESR), cation radical formation and its reactions were invest...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Adhikary A,Kumar A,Palmer BJ,Todd AD,Heizer AN,Sevilla MD

    更新日期:2014-06-01 00:00:00

  • Hydroxyl radical probe of protein surfaces using synchrotron X-ray radiolysis and mass spectrometry.

    abstract::A new approach is reported that combines synchrotron radiolysis and mass spectrometry to probe the structure of proteins. Hydroxyl radicals produced upon the radiolysis of protein solutions using synchrotron light modify amino acid side-chains on millisecond timescales. This results in the formation of stable oxidatio...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Kiselar JG,Maleknia SD,Sullivan M,Downard KM,Chance MR

    更新日期:2002-02-01 00:00:00

  • The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.

    abstract:PURPOSE:Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replicatio...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Nitsche M,Christiansen H,Hermann RM,Lucke EM,Peters K,Rave-Frank M,Schmidberger H,Pradier O

    更新日期:2008-08-01 00:00:00

  • EGF-coated gold nanoparticles provide an efficient nano-scale delivery system for the molecular radiotherapy of EGFR-positive cancer.

    abstract::Purpose Radiolabeled antibodies and peptides hold promise for molecular radiotherapy but are often limited by a low payload resulting in inadequate delivery of radioactivity to tumour tissue and, therefore, modest therapeutic effect. We developed a facile synthetic method of radiolabeling indium-111 (111In) to epiderm...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Song L,Falzone N,Vallis KA

    更新日期:2016-11-01 00:00:00

  • Lack of correlation between ATM protein expression and tumour cell radiosensitivity.

    abstract:PURPOSE:Cells derived from individuals in which the ataxia telangiectasia (ATM) gene is mutated are hypersensitive to ionizing radiation. Whether differences in ATM protein levels exist among human malignant glioma cell lines and whether such differences are correlated with cellular radiosensitivity were determined. M...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Chan DW,Gately DP,Urban S,Galloway AM,Lees-Miller SP,Yen T,Allalunis-Turner J

    更新日期:1998-08-01 00:00:00

  • Spin transfer from protein to DNA in X-irradiated 'dry' and hydrated chromatin: an electron spin resonance investigation of spectral components between 77 K and room temperature.

    abstract:PURPOSE:To investigate the potential total and relative free-radical transfer from histones to DNA in X-irradiated chromatin, by analysing the relative contributions of individual radicals from protein and from DNA. MATERIALS AND METHODS:Chromatin was isolated from calf thymus, freeze-dried and either used as such or ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Weiland B,Hüttermann J

    更新日期:2000-08-01 00:00:00

  • Kinetics of chromosome lesion repair in synchronized quiescent and proliferating CHO cells.

    abstract::The induction of chromosome aberrations by X-rays was investigated in synchronized quiescent and proliferating CHO-K1 cells. Kinetics of chromosome lesion repair was studied using the method of fractionated irradiation. In both cell types the time-course of repair during fractionation intervals followed first-order ki...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Volkmer B,Virsik-Peuckert RP

    更新日期:1990-12-01 00:00:00

  • Capabilities of the RENEB network for research and large scale radiological and nuclear emergency situations.

    abstract:PURPOSE:To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These ca...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Monteiro Gil O,Vaz P,Romm H,De Angelis C,Antunes AC,Barquinero JF,Beinke C,Bortolin E,Burbidge CI,Cucu A,Della Monaca S,Domene MM,Fattibene P,Gregoire E,Hadjidekova V,Kulka U,Lindholm C,Meschini R,M'Kacher R,Moquet

    更新日期:2017-01-01 00:00:00

  • Enhanced transplantability of a cell line from a murine ovary granulosa cell tumour in syngeneic B6C3F(1) mice continuously irradiated with low dose-rate gamma-rays.

    abstract:PURPOSE:To understand the mechanisms of life-shortening due to early neoplastic death caused by chronic low dose-rate (LDR; 20 mGy/22 h/day) radiation which accumulates to a high dose (HD; 8 Gy) (LDR/HD) as reported previously. MATERIALS AND METHODS:Female B6C3F(1) mice were continuously exposed to LDR/HD gamma-rays u...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Takai D,Todate A,Yanai T,Ichinohe K,Oghiso Y

    更新日期:2011-07-01 00:00:00

  • Effect of a 915-MHz simulated mobile phone signal on cognitive function in man.

    abstract:PURPOSE:To examine whether a simulated mobile telephone transmission at 915 MHz has an effect on cognitive function in man. MATERIALS AND METHODS:Thirty-six subjects in two groups were each given two training sessions and then three test sessions in a randomized three-way cross-over design. About 1 W mean power at 915...

    journal_title:International journal of radiation biology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Preece AW,Iwi G,Davies-Smith A,Wesnes K,Butler S,Lim E,Varey A

    更新日期:1999-04-01 00:00:00

  • Radiation response of mouse lymphoid and myeloid cell lines. Part III. Different signals can lead to apoptosis and may influence sensitivity to killing by DNA double-strand breakage.

    abstract::We have examined the timing of gamma-irradiation-induced death in relation to cell cycle progression using a panel of mouse lymphoid or myeloid cell lines. Death was found to occur immediately after irradiation ('rapid interphase' death), or after arrest in G2 phase ('delayed interphase' death). In part II of this ser...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Radford IR,Murphy TK

    更新日期:1994-02-01 00:00:00

  • Similarities in the repair kinetics of sublethal and potentially lethal X-ray damage in log phase Chinese hamster V79 cells.

    abstract::We have compared the repair kinetics of X-ray-induced sublethal damage (SLD) and potentially lethal damage (PLD) in V79 cells during postirradiation incubation in growth medium at 37 degrees C. Kinetics of SLD repair were studied by dose fractionation (D1 + D2 = 2 + 2, 4 + 2, 4 + 4, 10 + 4 and 10 + 7 Gy). Kinetics of ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Reddy NM,Lange CS

    更新日期:1989-09-01 00:00:00

  • Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction?

    abstract::Recent evidence indicates that isoeffect doses for spinal cord and kidney may be overestimated for fraction sizes as small as 1 or 2 Gy when calculated from a linear-quadratic (LQ) model fitted to data obtained for fraction sizes larger than 2 Gy. Reasons for this are unknown, but possible interpretations include exha...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Thames HD,Ang KK,Stewart FA,van der Schueren E

    更新日期:1988-07-01 00:00:00

  • Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.

    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


    authors: Cordes N,Plasswilm L,Bamberg M,Rodemann HP

    更新日期:2002-01-01 00:00:00

  • Cell signalling and radiation survival: the impact of protein phosphatases.

    abstract:PURPOSE:This review will examine the role of phosphatases in cancer cell signalling and also outline emerging findings regarding the influence of phosphatases on tumor cell survival after ionising radiation. CONCLUSION:The exposure of tumour cells to clinically relevant doses of ionising radiation causes DNA damage an...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章,评审


    authors: Hamilton J,Bernhard EJ

    更新日期:2009-11-01 00:00:00

  • Lethality of heavy ion-induced DNA double-strand breaks in mammalian cells.

    abstract::Cell killing and the production of DNA double-strand breaks (dsbs) were measured in parallel for V79 cells and a human tumour cell line (Caski) following exposure to radiations of differing linear energy transfer (LET) including accelerated heavy ions. Dsb induction was assessed by neutral filter elution (pH 7.4) and ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Weber KJ,Flentje M

    更新日期:1993-08-01 00:00:00

  • Detrimental effect of UV-B radiation on growth, photosynthetic pigments, metabolites and ultrastructure of some cyanobacteria and freshwater chlorophyta.

    abstract:BACKGROUND:Global warming directly influencing ozone layer depletion, which eventually is increasing ultraviolet radiation penetration having far-reaching impacts on living biota. This particularly influences the primary producer microalgae which are the basic unit of food webs in the aquatic habitats. Therefore, it is...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: El-Sheekh MM,Alwaleed EA,Ibrahim A,Saber H

    更新日期:2020-12-03 00:00:00

  • Expression of transforming growth factor-beta 1 in mouse skin during the acute phase of radiation damage.

    abstract::Transforming growth factor-beta (TGF beta 1) plays a central role in wound healing, so its perturbation by radiation may contribute to the acute and late effects seen in irradiated skin. TGF beta 1 mRNA expression was measured by PCR, in the skin of the CD1 and CBA mouse, exposed to Sr-90 beta from an 11-mm diameter s...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Randall K,Coggle JE

    更新日期:1995-09-01 00:00:00

  • Radiation-induced chromosomal instability in human fibroblasts: temporal effects and the influence of radiation quality.

    abstract:PURPOSE:To determine whether chromosomal instability is induced in human diploid fibroblasts by ionizing radiation and to investigate the effects of radiation quality by comparing X-rays, neutrons and alpha-particles. MATERIALS AND METHODS:Cells from two human diploid fibroblast lines, HF12 and HF19, were irradiated a...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Kadhim MA,Marsden SJ,Wright EG

    更新日期:1998-02-01 00:00:00

  • Efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) for the decorporation of uranium after intramuscular contamination in rats.

    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


    authors: Henge-Napoli MH,Ansoborlo E,Chazel V,Houpert P,Paquet F,Gourmelon P

    更新日期:1999-11-01 00:00:00

  • Hypoxia-specific inhibition of recovery from radiation damage by a novel 2-nitroimidazole with a theophylline side chain.

    abstract::A novel 2-nitroimidazole with a theophylline side-chain, 7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline, (NITP) was as efficient a hypoxic-cell radiosensitizer as misonidazole. However, if cells were irradiated with NITP under hypoxic conditions and then exposed to the drug under aerobic conditions, a much larger ra...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Hodgkiss RJ,Kelleher E,Parrick J

    更新日期:1992-06-01 00:00:00

  • Natural radionuclides in fish species from surface water of Bagjata and Banduhurang uranium mining areas, East Singhbhum, Jharkhand, India.

    abstract:PURPOSE:To study the natural radionuclides in the freshwater fish samples around the uranium mining areas of Bagjata and Banduhurang, East Singhbhum, Jharkhand, India. MATERIALS AND METHODS:The naturally occurring radioisotopes of uranium, U(nat), consisting of (234)U, (235)U and (238)U; (226)Ra, (230)Th and (210)Po w...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Giri S,Singh G,Jha VN,Tripathi RM

    更新日期:2010-11-01 00:00:00

  • Posterior subcapsular cataracts are a late effect after acute exposure to 0.5 Gy ionizing radiation in mice.

    abstract:PURPOSE:The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. MATERIAL AND METHODS:We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (60Co source; 0.063 Gy/min) at...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Kunze S,Cecil A,Prehn C,Möller G,Ohlmann A,Wildner G,Thurau S,Unger K,Rößler U,Hölter SM,Tapio S,Wagner F,Beyerlein A,Theis F,Zitzelsberger H,Kulka U,Adamski J,Graw J,Dalke C

    更新日期:2021-01-19 00:00:00

  • Cancer stem cells and radiotherapy.

    abstract:PURPOSE:The present work summarises the history and current status of research into the importance of cancer stem cells for radiobiological research and for clinical radiation oncology. An effort is made to differentiate clonogenicity from stemness of cancer cells. CONCLUSION:In radiooncology, cancer stem cells have b...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章,评审


    authors: Baumann M,Krause M,Thames H,Trott K,Zips D

    更新日期:2009-05-01 00:00:00

  • The relevance of tumour and surrounding normal tissue vascular density in clinical hyperthermia of locally advanced breast carcinoma.

    abstract::It follows from the present work that the vascularization of the normal tissue present in the treatment volume limits the temperatures achieved during heat treatment of invasive ductal breast carcinoma. The temperatures can often be increased by giving fractionated heat treatment because heat treatment may reduce the ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Lyng H,Monge OR,Bøhler PJ,Rofstad EK

    更新日期:1991-07-01 00:00:00

  • Relative toxicity of (45)Ca beta-particles and (242)Cm alpha-particles following their intravenous injection into mice as radiolabelled FAP.

    abstract:PURPOSE:To determine the relative toxicity of alpha- and beta-radiations under conditions of controlled temporal and spatial dose distribution. METHODS:Fused aluminosilicate particles were radiolabelled with either (45)Ca (a beta-emitter) or (242)Cm (an alpha-emitter). These were injected into CBA/Ca mice to give life...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Priest ND,Hoel DG,Brooks PN

    更新日期:2010-04-01 00:00:00

  • "In situ" observation of guanine radicals induced by ultrasoft X-ray irradiation around the K-edge regions of nitrogen and oxygen.

    abstract:PURPOSE:In order to understand the molecular mechanism of nucleobase damage caused by ultrasoft X-ray irradiation, guanine radicals have been studied using an X-band EPR (electron paramagnetic resonance) spectrometer installed in a synchrotron soft X-ray beamline. MATERIALS AND METHODS:Guanine pellets were irradiated ...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章


    authors: Yokoya A,Akamatsu K,Fujii K,Ukai M

    更新日期:2004-11-01 00:00:00

  • Nuclear structure and the microdistribution of radiation damage in DNA.

    abstract::Evidence for the roles of proteins and metal ions in the microheterogeneity of DNA damage is reviewed. Decondensation of chromatin in hypotonic buffers markedly sensitizes the DNA to radiation, while treatment of nuclei with hypertonic buffers strips the DNA of histones and other nuclear proteins and enhances the radi...

    journal_title:International journal of radiation biology

    pub_type: 杂志文章,评审


    authors: Oleinick NL,Balasubramaniam U,Xue L,Chiu S

    更新日期:1994-11-01 00:00:00