Showing papers in "International Journal of Radiation Biology in 2006"
Washington University in St. Louis1, Stanford University2, University of Texas MD Anderson Cancer Center3, University of Toronto4, University of Pennsylvania5, National Institutes of Health6, University of Washington7, University of Texas Southwestern Medical Center8, Mount Vernon Hospital9, Georgetown University10, St George's, University of London11, Johns Hopkins University12, Dartmouth College13, University of Mainz14
TL;DR: Recommendations are yielded on using hypoxia measurement to identify patients who would respond best to radiation therapy, which would improve treatment planning and represent a narrow focus, as hypoxIA measurement might also prove useful in drug development and in increasing the understanding of tumor biology.
Abstract: James L. Tatum, Cancer Imaging Program, Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI)Gary J. Kelloff, Cancer Imaging Program, Division of Cancer Treatment and D...
594 citations
TL;DR: Investigating quantitatively the induction and rejoining of DNA double strand breaks in V79-4 and xrs-5 Chinese hamster cells and HF19 human fibroblast cells using the phosphorylation of the histone protein H2AX (γ-H2AX) as an indicator of DSB found the variation in the rate of dephosphorylated of induced foci are dependent both on radiation quality and cell characteristics.
Abstract: Purpose: To investigate quantitatively the induction and rejoining of DNA double strand breaks (DSB) in V79-4 and xrs-5 Chinese hamster cells and HF19 human fibroblast cells, using the phosphorylat...
191 citations
TL;DR: Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups and made tardigradum sterile.
Abstract: Purpose: Tardigrades are known to survive high doses of ionizing radiation. However, there have been no reports about radiation effects in tardigrades under culture conditions. In this study, we investigated tolerance of the tardigrade, Milnesium tardigradum, against gamma-rays and heavy ions by determining short-term or long-term survival, and reproductive ability after irradiation.Materials and methods: Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 – 7000 Gy) or heavy ions (1000 – 8000 Gy) to evaluate short-term survival at 2, 24 and 48 h post-irradiation. Long-term survival and reproduction were observed up to 31 days after irradiation with gamma-rays (1000 – 4000 Gy).Results: At 48 h after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups. N...
175 citations
TL;DR: A literature review of candidate protein biomarkers for individual radiation biodosimetry of exposure to ionizing radiation found ATM (Ataxia telengiectasia mutated), H2AX (histone 2AX), CDKN1A (Cyclin-dependent kinase inhibitor 1A), and TP53 (tumor protein 53) are top candidate radiationprotein biomarkers.
Abstract: Purpose: To conduct a literature review of candidate protein biomarkers for individual radiation biodosimetry of exposure to ionizing radiation.Materials and methods: Reviewed ∼300 publications (1973 – April 2006) that reported protein effects in mammalian systems after either in vivo or in vitro radiation exposure.Results: We found 261 radiation-responsive proteins including 173 human proteins. Most of the studies used high doses of ionizing radiation (>4 Gy) and had no information on dose- or time-responses. The majority of the proteins showed increased amounts or changes in phosphorylation states within 24 h after exposure (range: 1.5- to 10-fold). Of the 47 proteins that are responsive at doses of 1 Gy and below, 6 showed phosphorylation changes at doses below 10 cGy. Proteins were assigned to 9 groups based on consistency of response across species, dose- and time-response information and known role in the radiation damage response.Conclusions: ATM (Ataxia telengiectasia mutated), H2AX (histone 2AX),...
173 citations
TL;DR: The previously observed associations with risk of radiation-induced subcutaneous fibrosis could not be replicated in the present study and further studies are needed to elucidate the influence of genetic variation upon normal tissue radiosensitivity.
Abstract: Purpose: In two previously published studies, associations with risk of radiation-induced subcutaneous fibrosis were found for single nucleotide polymorphisms (SNP) in TGFB1 (transforming growth factor beta 1 gene), XRCC1 (X-ray repair cross-complementing 1 gene), XRCC3 (X-ray repair cross-complementing 3 gene), SOD2 (manganese superoxide dismutase gene) and ATM (gene of ataxia telangiectasia mutated). The present study was conducted to seek a confirmation of these findings.Materials and methods: Like the 41 patients previously investigated, the 120 subjects included in the present study were accrued from a historical cohort of 319 post-mastectomy radiotherapy patients. All patients received hypo-fractionated radiotherapy. The TGFB1 position −509, codons 10 and 25, XRCC1 codons 194, 280 and 399, XRCC3 codon 241, SOD2 codon 16, ATM codon 1853 and APEX (apurinic/apyrimidinic exonuclease gene) codon 148 polymorphisms were assessed based on archival histological material. Differences in fibrosis risk were qua...
106 citations
DSM1
TL;DR: The observation that thymidine and 2′-deoxyguanosine are equally damaged rules out a major contribution of the direct ionization in radiation-induced base damage to both isolated and cellular DNA by heavy ions.
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) γ-rays.Material and Methods: DNA samples and human monocytes were exposed either to γ-rays emitted by a 60Co source or to 12C6+ or 36Ar18+ ions. The levels of thymidine and 2′-deoxyguanosine oxidation products were determined by liquid chromatography coupled to tandem mass spectrometry subsequently to DNA digestion into nucleosides.Results: The yields of thymidine lesions were similar to those of 8-oxo-7,8-dihydro-2′-deoxyguanosine within isolated DNA exposed either to γ-rays or argon ions. Addition of spermine and Tris aimed at minimizing the indirect effect modified this ratio to the same extent with both types of radiation. In cells, the level of radiation-induced base damage was found to...
96 citations
TL;DR: A meta-analysis of data from in vitro studies and short-term animal studies that have combined extremely low frequency magnetic fields with known carcinogens or other toxic physical or chemical agents suggests the radical pair mechanism is a good candidate mechanism for explaining the biphasic dose-response seen in the present analysis.
Abstract: Purpose: This paper is a meta-analysis of data from in vitro studies and short-term animal studies that have combined extremely low frequency magnetic fields with known carcinogens or other toxic physical or chemical agents.Materials and methods: The data was analyzed by systematic comparison of study characteristics between positive and negative studies to reveal possible consistent patterns.Results: The majority of the studies reviewed were positive, suggesting that magnetic fields do interact with other chemical and physical exposures. Publication bias is unlikely to explain the findings. Interestingly, a nonlinear ‘dose-response’ was found, showing a minimum percentage of positive studies at fields between 1 and 3 mT. The radical pair mechanism (magnetic field effects on recombination of radical pairs) is a good candidate mechanism for explaining the biphasic dose-response seen in the present analysis.Conclusions: Most of the studies reviewed used magnetic fields of 100 μT or higher, so the findings a...
90 citations
TL;DR: This study shows that similar bystander signalling pathways leading to apoptosis are induced following microbeam irradiation and following medium transfer, demonstrating that the mechanisms involved are common across different radiation qualities and conditions and indicates that they may be relevant in vivo.
Abstract: Purpose: There is now no doubt that bystander signalling from irradiated cells occurs and causes a variety of responses in cells not targeted by the ionizing track However, the mechanisms underlying these processes are unknown and the relevance to radiotherapy and risk assessment remains controversial Previous research by our laboratory has shown bystander effects in a human keratinocyte cell line, HPV-G cells, exposed to medium from γ irradiated HPV-G cells The aim of this work was to investigate if similar mechanisms to those identified in medium transfer experiments occurred in these HPV-G cells when they are in the vicinity of microbeam irradiated cells Demonstration of a commonality of mechanisms would support the idea that the process is not artifactualMaterials and methods: HPV-G cells were plated as two separate populations on mylar dishes One population was directly irradiated using a charged particle microbeam (1 – 10 protons) The other population was not irradiated Bystander factor-indu
76 citations
TL;DR: It is demonstrated that a single exposure to 5 Gy of X rays leads to noticeable epigenetic changes in the rat mammary gland that occurred in the context of activation of DNA damage repair and alterations in the pro-survival growth-stimulatory cellular signaling pathways.
Abstract: Purpose: Ionizing radiation is a potent mammary gland carcinogen, yet the exact molecular etiology of radiation-induced breast cancer remains unknown.Materials and methods: Our study utilized a rat model of breast carcinogenesis to analyse the molecular and epigenetic changes induced in mammary gland tissue upon exposure to ionizing radiation (IR). Using a methylation-sensitive cytosine extension assay we studied the IR-induced changes in DNA methylation. In parallel, we analysed the expression of proteins involved in DNA methylation, DNA repair and cell proliferation control. Molecular changes were related to cellular proliferation and apoptosis.Results: We found that IR led to a loss of genomic cytosine methylation in the exposed mammary tissue. Global DNA hypomethylation was paralleled by reduction in the levels of maintenance (DNMT1) and de novo (DNMT3a and 3b) DNA methyltransferases and methyl-binding protein MeCP2. The observed DNA hypomethylation was linked, at least in part, to activation of DNA r...
69 citations
TL;DR: Total nighttime melatonin output is unchanged by mobile phone handset emissions, but there could be an effect on melatonin onset time.
Abstract: Purpose: To test whether exposure to the emissions from a digital mobile phone handset prior to sleep alters the secretion of melatonin.Materials and methods: In a double-blind cross-over design, 55 adult volunteers were both actively exposed or sham-exposed (in random order on successive Sunday nights) to mobile phone emissions for 30 min (0.25 W average power). Urine collection occurred immediately prior to retiring to bed and on rising the next morning. Melatonin output was estimated from principal metabolite concentrations (6-sulphatoxymelatonin (aMT6s) via radioimmunoassay), urine volumes and creatinine concentrations.Results: Total melatonin metabolite output (concentration×urine volume) was unchanged between the two exposure conditions (active 14.1±1.1 μg; sham 14.6±1.3 μg). The pre- and post-bedtime outputs considered separately were also not significantly different, although the pre-bedtime value was less for active versus sham exposure. When melatonin metabolite output was estimated from the rat...
68 citations
TL;DR: This study comprehensively examined whether a 24-h continuous exposure to a 935 MHz GSM basic signal delivering SAR of 1 or 2 W/Kg is genotoxic per se or whether, it can influence the genotoxicity of the well-established clastogenic agent; x-radiation.
Abstract: Purpose: The possibility of genotoxicity of radiofrequency radiation (RFR) applied alone or in combination with x-rays was investigated in vitro using several assays on human lymphocytes. The chosen specific absorption rate (SAR) values are near the upper limit of actual energy absorption in localized tissue when persons use some cellular telephones. The purpose of the combined exposures was to examine whether RFR might act epigenetically by reducing the fidelity of repair of DNA damage caused by a well-characterized and established mutagen.Methods: Blood specimens from 14 donors were exposed continuously for 24 h to a Global System for Mobile Communications (GSM) basic 935 MHz signal. The signal was applied at two SAR; 1 and 2 W/Kg, alone or combined with a 1-min exposure to 1.0 Gy of 250 kVp x-rays given immediately before or after the RFR. The assays employed were the alkaline comet technique to detect DNA strand breakage, metaphase analyses to detect unstable chromosomal aberrations and sister chromat...
TL;DR: It is suggested that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.
Abstract: Purpose: To assess cancer risks in a population that received prolonged low dose-rate γ-irradiation for about 10 years as a result of occupying buildings containing 60Co-contaminated steel in Taiwa...
TL;DR: The current findings suggest that EMF emitted by mobile phones has effects on brain oscillatory responses during cognitive processing in children.
Abstract: Purpose: To assess the effects of electromagnetic fields (EMF) emitted by mobile phones (MP) on the 1 – 20 Hz event-related brain oscillatory EEG (electroencephalogram) responses in children performing an auditory memory task (encoding and recognition).Materials and methods: EEG data were gathered while 15 subjects (age 10 – 14 years) performed an auditory memory task both with and without exposure to a digital 902 MHz MP in counterbalanced order.Results: During memory encoding, the active MP modulated the event-related desynchronization/synchronization (ERD/ERS) responses in the ∼4 – 8 Hz EEG frequencies. During recognition, the active MP transformed these brain oscillatory responses in the ∼4 – 8 Hz and ∼15 Hz frequencies.Conclusions: The current findings suggest that EMF emitted by mobile phones has effects on brain oscillatory responses during cognitive processing in children.
TL;DR: The microbeam irradiation is useful in characterizing tissue-specific, local biological response to radiation in organisms, and DNA damage-induced cell cycle arrest and apoptosis were observed in locally irradiated regions, but there was little, if any, ‘bystander effect’ in the nematode.
Abstract: Purpose: To investigate positional effects of radiation with an energetic heavy-ion microbeam on germline cells using an experimental model metazoan Caenorhabditis elegans.Materials and methods: The germline cells were irradiated with raster-scanned broad beam or collimated microbeam of 220 MeV 12C5+ particles delivered from the azimuthally varying field (AVF) cyclotron, and subsequently observed for cell cycle arrest and apoptosis.Results: Whole-body irradiation with the broad beam at the L4 larval stage arrested germ cell proliferation. When the tip region of the gonad arm was irradiated locally with the microbeam at the L4 stage, the same arrest was observed. When the microbeams were used to irradiate the pachytene region of the gonad arm, at a young gravid stage, radiation-induced apoptosis occurred in the gonad. In contrast, arrest and apoptosis were not induced in the non-irradiated neighboring region or the opposite gonad. Similar results were confirmed in the c-abl-1 (mammalian ortholog of cellula...
TL;DR: Results showed that, under the conditions of the present experiment, MW-exposure (either CW or GSM-900) does not significantly increase the apoptosis rate in the human neuroblastoma cell line SH-SY5Y.
Abstract: Purpose:The aim of this study was to investigate microwave (MW) effects on neuronal apoptosis in vitro.Materials and methods:Human neuroblastoma cells SH-SY5Y were exposed to a 900 MHz global system for mobile communication (GSM) or continuous-wave (CW) radiofrequency fields for 24 h in a wire-patch cell. The specific absorption rates (SAR) used were 2 W/kg for CW and 0.25 W/kg average for GSM. During CW exposure, an increase of 2°C was measured, and controls with cells exposed to 39°C were then performed. Apoptosis rate was assessed immediately or 24 h after exposure using three methods: (i) 4′,6-diamino-2-phenylindole (DAPI) staining; (ii) flow cytometry using double staining with TdT-mediated dUTP nick-end labeling (TUNEL) and propidium iodide (PI); and (iii) measurement of caspase-3 activity by fluorimetry.Results:No statistically significant difference in the apoptosis rate was observed between sham and 24 h MW-exposed cells, either GSM-900 at an average SAR of 0.25 W/kg, or CW 900 MHz at a SAR of 2 ...
TL;DR: Results indicate that anhydrobiosis enhances radiotolerance, resulting in increases of successful metamorphoses, and did not protect against radiation damage in terms of producing viable offspring.
Abstract: Purpose: Anhydrobiotic organisms are known to have an extremely high tolerance against a range of stresses. However, the functional role of anhydrobiosis in radiation tolerance is poorly understood, especially in development following irradiation. The present study aims to evaluate effects of anhydrobiosis on radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki.Materials and methods: Larval survival (48 h), anhydrobiotic ability, metamorphosis and reproduction after exposure to 1 – 9000 Gy of gamma-rays at the larval stage were compared between anhydrobiotic (dry) and normal (wet) phases.Results: Wet larvae were killed in a dose-dependent manner at doses higher than 2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at 48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis di...
TL;DR: Gamma irradiation may play a role in Th1 and Th2 cytokine expression, via regulation of the level of cytokine-mediators through transcriptional modulation and Stat signaling, and results are helpful to understand general profile of cytokines expression in response to gamma irradiation.
Abstract: Purpose: The expression of cytokine mRNA and their related transcription factors was examined in order to assess the effects of gamma radiation on the immune function of murine splenocytes.Materials and methods: Splenocytes were collected from seven-week-old female Balb/c mice, and then irradiated at a dose of 5 Gy of 60Co γ-ray at a dose rate of 1.394 Gy/min. Total RNA was extracted from both irradiated and non-irradiated splenocytes at 1/2, 1, 3, 6, and 24 h and analysed by reverse transcription-polymerase chain reaction (RT-PCR).Results: The mRNA level of interferon (IFN)-γ, which is a Th1-type (T helper cell type 1) cytokine, was reduced after 3 h post-irradiation, whereas the interleukin (IL)-2 mRNA in the naive splenocytes had no significant changes within the 24 h after irradiation. Moreover, IFN-γ and IL-2 mRNA expression in concanavalin A (Con A, 2.5 μg/ml) activated-splenocytes was significantly reduced by gamma irradiation. On the other hand, the mRNA level of the Th2 type (T helper cell type 2...
TL;DR: The results reveal the high in vivo sensitivity of p53-dependent transcriptional activation of genes involved in the two main apoptotic pathways, their stimulation preceding the induction of apoptosis.
Abstract: Purpose: γ-irradiation leads to activation of p53 tumour suppressor gene and to p53-dependant stimulation of a large panel of cellular genes including proapoptotic genes involved in intrinsic and extrinsic pathways. Most in vivo published data referred to high (lethal) irradiation doses. The present study was performed to analyse the p53-dependent response to more relevant low irradiation doses.Materials and methods: Mice were whole body exposed to irradiation doses decreasing from 5 – 0.05 Gy. Gene expression was estimated by real time reverse transcriptase polymerase chain reaction measurements on RNA extracted from thymus and spleen. Apoptosis was evaluated by the percentage of either annexin V positive or sub-G1 cells.Results: A 0.1 Gy irradiation dose already gives a significant stimulation of Puma (p53 up-regulated modulator of apoptosis), and 0.2 Gy of Bax (Bcl-2-associated X protein) and Killer/DR5 (Death Receptor 5). The expression of genes involved in the two apoptotic pathways was induced as so...
TL;DR: The reversal of the levels of endogenous antioxidant enzymes and lipid peroxidation indicates reduced oxidative stress in CDF1 treated surviving mice, and the optimum dose, time and route of drug administration for maximum radioprotection byCDF1 were determined.
Abstract: Purpose: To evaluate and optimize the radioprotective ability of the most potent fraction of an aqueous extract of Coronopus didymus in whole body γ-irradiated Swiss albino mice and to evaluate the...
TL;DR: Melatonin administration prior to X-ray irradiation prevented radiation-induced oxidative damage during the reproductively active phase of the seasonally breeding rodent suggesting a high protective role of melatonin following X-Ray irradiation.
Abstract: Purpose: Biological effects of X-ray irradiation and protection by melatonin on the immune status of a tropical rodent, Funambulus pennanti, was examined by estimating oxidative damage of peripheral blood and spleen and protection by melatonin treatment.Material and methods: Seventy squirrels were divided into 4 sets of 25, 25, 10 and 10 having subdivisions into a total of eight groups. Squirrels of set 1 (groups A and B) received only normal saline, set 2 (groups C and D) received 25 μg/100 g body weight (bwt) melatonin and set 3 (groups E and F) received 25 μg/100 g bwt vitamin E for four weeks. Groups G and H of set 4 received high doses of melatonin (0.5 mg/100 g bwt) 30 min prior to and 30 min after X-ray irradiation, respectively, and were sacrificed 1 h after irradiation. Groups B and D were sacrificed after 4 h, 24 h, 48 h and 72 h of irradiation for total leukocyte count (TLC) in peripheral blood, percent apoptotic cells and lipid peroxidation (LPO) in spleen while group F was sacrificed after 4 ...
TL;DR: These results provide further support for the importance of redox state in the regulation of neural precursor cell function, and suggest that oxidative stress can inhibit the proliferative potential of cells through different mechanisms.
Abstract: Purpose: To determine whether changes in oxidative stress could enhance the sensitivity of neural precursor cells to ionizing radiation.Materials and methods: Two strategies were used whereby oxidative stress was modulated endogenously, through manipulation cell culture density, or exogenously, through direct addition of hydrogen peroxide.Results: Cells subjected to increased endogenous oxidative stress through low-density growth routinely exhibited an inhibition of growth following irradiation. However, cells subjected to chronic exogenous oxidative treatments showed increased sensitivity to proton and γ-irradiation compared to untreated controls. Reduced survival of irradiated cultures subjected to oxidizing conditions was corroborated using enzymatic viability assays, and was observed over a range of doses (1 – 5 Gy) and post-irradiation re-seeding densities (20 – 200 K/plate).Conclusions: Collectively our results provide further support for the importance of redox state in the regulation of neural pre...
TL;DR: CDH6 gene can be specifically up-regulated by low dose irradiation, and its inducible expression could be involved in a low dose hypersensitive response.
Abstract: Purpose: To identify candidate genes specifically involved in response to low-dose irradiation in human lymphoblastoid cells; to better clarify the role of the human chromodomain helicase DNA binding protein 6 gene (CHD6), one of these genes, in cell proliferation and radiosensitivity.Materials and methods: DNA microarray technology was used to analyse global transcriptional profile in human lymphoblastoid AHH-1 cells at 4 h after exposure to 0.5 Gy of γ-ray. Gene expression changes were confirmed by semi-quantitative reverse transcription – polymerase chain reaction (RT-PCR) and Northern blot. RNA interfering technology was employed to knock-down the CHD6 gene in A549 cells. Colony-forming ability was used to analyse radiosensitivity.Results: The microarray assay revealed a set of 0.5 Gy-responsive genes, including 30 up-regulated genes and 45 down-regulated genes. The up-regulated genes include a number of genes involved in: signal transduction pathways, e.g., STAT3, CAMKK2, SIRT1, CREM, MAPK3K7IP2 and ...
TL;DR: Time and temperature dependent in vitro cell responses to ionizing radiation and water-bath hyperthermia reveal time and temperature based responses to apoptosis and necrosis.
Abstract: Purpose: The purpose of the study was to examine the optimal time of exposure and dose of heat and ionizing radiation that results in the killing of human cancer cells in vitro via apoptosis vs. necrosis.Materials and methods: Human mammary carcinoma, colorectal carcinoma and normal bovine capillary endothelial (BCE) cell lines were subjected to 20 Gy ionizing radiation and 6, 12, 24, and 72 h later assessed for apoptosis using detection of apoptotic bodies and caspase assays. Necrosis was detected by loss of cells from the surface and lactate dehydrogenase (LDH) release. The colorectal carcinoma cells were subjected to hyperthermia using temperatures ranging from 39 – 44°C for 5, 15 or 45 min. exposures and at varying times post-treatment, apoptosis and necrosis were measured.Results: In response to ionizing radiation, none of the cells underwent necrosis and some cell types apoptosed 24 and 72 h posttreatment. The colorectal cancer cells exhibited a steady increase of apoptosis at 6, 12, and 24 h. When ...
TL;DR: It appears that protons reduce the number of HTB140 cells by apoptosis as well as by severe DNA damage, while γ-rays eliminate viable cells primarily by the production of irreparable DNA damage.
Abstract: Purpose: To measure the ability of protons and γ-rays to effect cell viability and cell survival of human HTB140 melanoma cells.Materials and methods: Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons or with 60Co γ-rays with single doses, ranging from 8 – 24 Gy. Cell viability using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay was evaluated at 6 h, 24 h, 48 h or 7 days after irradiation and clonogenic survival was assessed at 7 days after irradiation. Cell cycle phase redistribution and the level of apoptosis were evaluated at 6 h and 48 h after irradiation.Results: The study of cell viability as a function of time (cell survival progression) and cell survival, using a clonal assay, demonstrated the considerably stronger inactivation effect of protons compared to γ-rays with a relative biological effectiveness (RBE) of ∼1.64. Cell cycle phase distribution and apoptosis levels with time enabled us to investigate the deve...
TL;DR: Data show that chromosomal domains do not have a significant influence on fragment-size distribution, while the presence of DNA loops increases the frequencies of smaller fragments by nearly 30% for fragment sizes in the range from 2 kbp (bp = base pair) to 20 kbp.
Abstract: Purpose: To apply a polymer model of DNA damage induced by high-LET (linear energy transfer) radiation and determine the influence of chromosomal domains and loops on fragment length distribution.Materials and methods: The yields of DSB (double-strand breaks) induced by high-LET radiation were calculated using a track structure model along with a polymer model of DNA packed in the cell nucleus. The cell nucleus was constructed to include the chromosomal domains and chromatin loops. The latter were generated by the random walk method.Results and conclusions: We present data for DSB yields per track per cell, DNA fragment sizes, the radial distribution of DSB with respect to the track center, and the distribution of 0, 1, 2, and more DSB from a single particle. Calculations were carried out for a range of particles including He (40 keV/μm), N (225 keV/μm), and Fe ions (150 keV/μm). Situations relevant to PFGE (pulsed-field gel electrophoresis) and microbeam experiments with direct irradiation of the cell nu...
TL;DR: Constitutive expression of DNA repair-related genes may affect the development of acute side effects in radiotherapy patients, and high expression levels of these genes seem to support protection from adverse reactions.
Abstract: Purpose: Repair of radiation-induced DNA damage is believed to play a critical role in the development of adverse reactions in radiotherapy patients. Constitutive mRNA expression of repair genes was investigated in such patients to analyze whether expression patterns are predictive for therapy-related acute side effects.Materials and methods: Prostate cancer patients (n = 406) receiving intensity-modulated radiotherapy were recruited in a prospective epidemiological study. Adverse effects were monitored during therapy using common toxicity criteria. For expression analyses, samples from 58 patients were selected according to their observed grade of clinical side effects to radiotherapy. Expression profiles were generated from peripheral blood lymphocytes using customized cDNA-arrays which carried probes for 143 DNA repair or repair-related genes. In addition, expression of selected genes was confirmed by quantitative real-time reverse transcription PCR (RT-PCR). Constitutive mRNA expression profiles were ...
TL;DR: This study demonstrates that EAP protects mouse bone marrow cells against radiation-induced chromosomal aberrations and this reduction in radiation- induced chromosome damage may be due to free radical scavenging and reduction in lipid peroxidation.
Abstract: Purpose: Normal tissue radiosensitivity is the major limiting factor in radiotherapy of cancer. The use of phytochemicals may reduce the adverse effects of radiation in normal tissue. The effect of ethyl acetate fraction of Aphanamixis polystachya (EAP) was investigated on the radiation-induced chromosome damage in the bone marrow cells of Swiss albino mice exposed to various doses of γ-radiation.Materials and methods: The mice were divided into two groups, one group was exposed to 0, 1, 2, 3, 4 or 5 Gy of γ-radiation, while another group received 7.5 mg/kg body weight (BW) of EAP 1 h before exposure to 0, 1, 2, 3, 4 or 5 Gy of γ-radiation. Various asymmetrical chromosome aberrations were studied in the bone marrow cells of mice at 12, 24 or 48 h post-irradiation. To understand the mechanism of action of the free radical scavenging activity of 0, 5, 10, 20, 30, 40, 50, 60 or 70 μg/ml EAP, assays were carried out in vitro.Results: Irradiation of mice to different doses of gamma radiation caused a dose depe...
TL;DR: In this article, the authors showed that a dose of at least 10 Gy was sufficient to inhibit proliferation of KHYG-1 within the first day but not its cytolytic activity.
Abstract: Purpose: To evaluate γ-irradiation on KHYG-1, a highly cytotoxic natural killer (NK) cell line and potential candidate for cancer immunotherapy.Methods and materials: The NK cell line KHYG-1 was irradiated at 1 gray (Gy) to 50 Gy with γ-irradiation, and evaluated for cell proliferation, cell survival, and cytotoxicity against tumor targets.Results: We showed that a dose of at least 10 Gy was sufficient to inhibit proliferation of KHYG-1 within the first day but not its cytolytic activity. While 50 Gy had an apoptotic effect in the first hours after irradiation, the killing of K562 and HL60 targets was not different from non-irradiated cells but was reduced for the Ph + myeloid leukemia lines, EM-2 and EM-3.Conclusions: γ-irradiation (at least 10 Gy) of KHYG-1 inhibits cell proliferation but does not diminish its enhanced cytolytic activity against several tumor targets. This study suggests that KHYG-1 may be a feasible immunotherapeutic agent in the treatment of cancers.
TL;DR: Soluble factors released from irradiated lymphocytes initiate a signaling cascade in unirradiated lymphocyte resulting in increased response to mitogen and radioresistance which may have an important role in radiation-induced immunomodulation.
Abstract: Purpose: To study the bystander effects of γ-radiation in murine lymphocytes using irradiated conditioned medium (ICM) generated from irradiated lymphocytes.Methods: Proliferation response of unirradiated lymphocytes to mitogen concanavalin A (con A) in presence of ICM, collected from γ-irradiated lymphocytes (60Co source; 0.35 Gy/min; 0.1 – 1 Gy), was studied by 3H-thymidine incorporation and also by dye dilution using carboxyfluorescein succinimidyl ester (CFSE). Expression of proliferation markers, interleukin 2 receptor α chain (CD25) and cyclin D in ICM treated lymphocytes was analyzed by labeling with specific antibodies. Intracellular reactive oxygen species (ROS) and apoptosis were estimated by flow cytometry using dichlorodihydrofluorescein diacetate (H2DCFDA) and propidium iodide, respectively. Nitric oxide (NO) was measured using Griess reagent.Results: Proliferation response to con A in unirradiated lymphocytes was enhanced in the presence of ICM with maximum enhancement observed in the presen...
TL;DR: To compare the efficiency of different cytogenetic tools in estimating the doses received by four people involved in the Lilo accident and to monitor the dose estimate over 4.5 years, good stability of translocations is revealed.
Abstract: Purpose: To compare the efficiency of different cytogenetic tools in estimating the doses received by four people involved in the Lilo accident and to monitor the dose estimate over 4.5 years.Materials and methods: Several young Georgian frontier guards handled at least one of the 12 Caesium sources found in a former Russian military camp. Overexposure lasted from July 1996 to May 1997. The Institute for Radiological Protection and Nuclear Safety (IRSN) obtained blood samples taken at several intervals post-exposure from the four most highly-exposed people. Dose estimation was performed using dicentric and translocation scoring.Results: The first dose estimations performed by dicentric scoring gave whole-body doses ranging from 0.4 to 1.3 Gy. Overexposure was complex and several mathematical models were used to take this complexity into account. This could provide information concerning the circumstances of overexposure. Concerning follow-up, the yield of dicentrics decreased by about 50% in the first 4 m...