Efecte biològic dels raigs X de baixa energia, utilitzats en mamografies

Actualment s'assumeix que tots els raigs X, independentment de la seva energia, tenen el mateix efecte. Tot i així, hi ha estudis científics que ho qüestionen, i indiquen que els raigs X de baixa energia (com els que s'utilitzen en les mamografies) podrien tenir un efecte superior a l'assumit fins ara. Investigadors del grup de recerca d'"Estudis citogenètics i moleculars dels efectes de les radiacions ionitzants i del càncer" de la UAB han avaluat el dany produït pels raigs X de 30 kVp i els seus resultats semblen indicar que és superior al produït per raigs X d'energies més elevades.Actualmente se asume que todos los rayos X, independientemente de su energía, tienen el mismo efecto. Sin embargo, hay estudios científicos que lo cuestionan e indican que los rayos X de baja energía (como los que se utilizan en las mamografías) podrían tener unefecto superior que el asumido hasta ahora. Investigadores del grupo de investigación "Estudios citogenéticos y moleculares de los efectos de las radiaciones ionizantes y del cáncer"de la UAB han evaluado el daño producido por rayos X de 30 kVp y sus resultados parecen indicar que es superior al producido por rayos X de energías más elevadas

A New Model of Biodosimetry to Integrate Low and High Doses

Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy,the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberrationamong-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation

Cell to Cell Variability of Radiation-Induced Foci : relation between Observed Damage and Energy Deposition

Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to calculate a volume of 1.6 μm3 for which the spread of the specific energy distribution could explain the entire variability of RIF counts per cell in an exposed cell population. The definition of this volume may allow to use a microdosimetric quantity to predict heterogeneity in DNA damage. Moreover, this value is consistent with the order of magnitude of the volume occupied by the hydrated sugar-phosphate backbone of the DNA molecule, which is the part of the DNA molecule responsible for strand breaks

Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA

Essentials The Royal disease (RD) is a form of hemophilia B predicted to be caused by a splicing mutation. We generated an iPSC-based model of the disease allowing mechanistic studies at the RNA level. F9 mRNA analysis in iPSC-derived hepatocyte-like cells showed the predicted abnormal splicing. Mutated F9 mRNA level was very low but we also found traces of wild type transcripts. SUMMARY: Background The royal disease is a form of hemophilia B (HB) that affected many descendants of Queen Victoria in the 19th and 20th centuries. It was found to be caused by the mutation F9 c.278-3A>G. Objective To generate a physiological cell model of the disease and to study F9 expression at the RNA level. Methods Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs). Both the patient's and mother's iPSCs were differentiated into hepatocyte-like cells (HLCs) and their F9 mRNA was analyzed using next-generation sequencing (NGS). Results and Conclusion We demonstrated the previously predicted aberrant splicing of the F9 transcript as a result of an intronic nucleotide substitution leading to a frameshift and the generation of a premature termination codon (PTC). The F9 mRNA level in the patient's HLCs was significantly reduced compared with that of his mother, suggesting that mutated transcripts undergo nonsense-mediated decay (NMD), a cellular mechanism that degrades PTC-containing mRNAs. We also detected small proportions of correctly spliced transcripts in the patient's HLCs, which, combined with genetic variability in splicing and NMD machineries, could partially explain some clinical variability among affected members of the European royal families who had lifespans above the average. This work allowed the demonstration of the pathologic consequences of an intronic mutation in the F9 gene and represents the first bona fide cellular model of HB allowing the study of rare mutations at the RNA level

A Natural Human Retrovirus Efficiently Complements Vectors Based on Murine Leukemia Virus

Background: Murine Leukemia Virus (MLV) is a rodent gammaretrovirus that serves as the backbone for common gene delivery tools designed for experimental and therapeutic applications. Recently, an infectious gammaretrovirus designated XMRV has been identified in prostate cancer patients. The similarity between the MLV and XMRV genomes suggests a possibility that the two viruses may interact when present in the same cell. Methodology/Principal Findings: We tested the ability of XMRV to complement replication-deficient MLV vectors upon coinfection of cultured human cells. We observed that XMRV can facilitate the spread of these vectors from infected to uninfected cells. This functional complementation occurred without any gross rearrangements in the vector structure, and the co-infected cells produced as many as 10 4 infectious vector particles per milliliter of culture medium. Conclusions/Significance: The possibility of encountering a helper virus when delivering MLV-based vectors to human cells in vitro and in vivo needs to be considered to ensure the safety of such procedures

Concentration-Dependent Protection by Ethanol Extract ofPropolis against γ-Ray-Induced Chromosome Damage in HumanBlood Lymphocytes

[EN] Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 ¿g mL-1 and then exposed to 2 Gy ¿-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 ¿g mL-1 of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation. Copyright © 2011 A. Montoro et al.This research was supported in part by the Company Dieteticos Intersa S.A., U.P.V., and Hospital Universitario La Fe of Valencia and Consejo de Seguridad Nuclear (2696/SRO). The authors express their appreciation to Dr. Pepe Perez (Hospital Universitario La Fe) and Dr. Alberto Yuste (U.P.V.).Montoro, A.; Barquinero, J.; Almonacid, M.; Montoro, A.; Sebastià, N.; Verdú Martín, GJ.; Sahuquillo, V.... (2011). Concentration-Dependent Protection by Ethanol Extract ofPropolis against γ-Ray-Induced Chromosome Damage in HumanBlood Lymphocytes. Evidence-based Complementary and Alternative Medicine. 1-7. doi:10.1155/2011/174853S1

Módulos MMIC multifunción para aplicaciones espaciales

This paper presents the design of multifunction monolithic microwave integrated circuits (MMIC) to be used in transmit/receive modules for onboard satellite applications. Two chips have been developed: one for frequency generation including a negatron VCO, a frequency tripler and a digital frequency divider, and a second for signal amplification and conversion including AGC amplifiers and mixers. The goal of the work is to reduce the number and size (and consequently the cost) of the circuitry actually in use, without sacrificing system performance, through the use of a mature GaAs PHEMT technology. Issues such as suitable circuit topologies, dc power consumption, circuit area minimization and optimization are all important factors addressed during the project

Retrospective biodosimetry using translocation frequency in a stable cell of occupationally exposed to ionizing radiation

Two cases of hematological malignancies were reported in an industrial radiography company over a year, which were reasonably suspected of being consequences of prolonged exposure to ionizing radiation because of the higher incidence than expected in the general population. We analyzed chromosomal aberrations in the peripheral blood lymphocytes from the other workers who had been working under similar circumstances as the patients in the company. Among the subjects tested, 10 workers who belonged to the highest band were followed up periodically for 1.5 years since the first analysis. The aim of this study was to clarify pertinence of translocation analysis to an industrial set-up where chronic exposure was commonly expected. To be a useful tool for a retrospective biodosimetry, the aberrations need to be persistent for a decade or longer. Therefore we calculated the decline rates and half-lives of frequency for both a reciprocal translocation and a dicentric chromosome and compared them. In this study, while the frequency of reciprocal translocations was maintained at the initial level, dicentric chromosomes were decreased to 46.9% (31.0-76.5) of the initial frequency over the follow-up period. Our results support the long-term stability of reciprocal translocation through the cell cycle and validate the usefulness of translocation analysis as a retrospective biodosimetry for cases of occupational exposure

Review of retrospective dosimetry techniques for external ionising radiation exposures

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. © The Author 2010. Published by Oxford University Press. All rights reserved