Establishment and validation of surface model for biodosimetry based on γ-H2AX foci detection.

INTRODUCTION: In the event of a radiation accident detecting γ-H2AX foci is being accepted as fast method for triage and dose assessment. However, due to their disappearance kinetics, published calibrations have been constructed at specific post-irradiation times. OBJECTIVES: To develop a surface, or tridimensional, model to estimate doses at times not included in the calibration analysis, and to validate it. MATERIALS AND METHODS: Calibration data was obtained irradiating peripheral mononucleated cells from one donor with radiation doses ranging from 0 to 3 Gy, and γ -H2AX foci were detected microscopically using a semi-automatic method, at different post-irradiation times from 0.5 to 24 h. For validation, in addition to the above-mentioned donor, blood samples from another donor were also used. Validation was done within the range of doses and post-irradiation times used in the calibration. RESULTS: The calibration data clearly shows that at each analyzed time, the γ-H2AX foci frequency increases as dose increases, and for each dose this frequency decreases with post-irradiation time. The γ-H2AX foci nucleus distribution was clearly overdispersed, for this reason to obtain bidimensional and tridimensional dose-effect relationships no probability distribution was assumed, and linear and non-linear least squares weighted regression was used. In the two validation exercises for most evaluated samples, the 95% confidence limits of the estimated dose were between ±0.5 Gy of the real dose. No major differences were observed between donors. CONCLUSION: In case of a suspected overexposure to radiation, the surface model here presented allows a correct dose estimation using γ-H2AX foci as biomarker. The advantage of this surface model is that it can be used at any post-irradiation time, in our model between 0.5 and 24 h.

Graft reduction surgery is associated with poorer outcome after lung transplantation: a single-centre propensity score-matched analysis.

OBJECTIVES: Implanted lung volume-reduction surgery due to donor/recipient size mismatch could affect both lung function and survival. We examined the outcomes of lung volume-reduction procedures post-lung transplant. METHODS: We retrospectively reviewed 366 consecutive adult lung transplants carried out between January 2014 and December 2018 at one single centre. Patients were divided into either a non-reduced-size lung transplant or a reduced-size lung transplant (RT) group. To adjust for covariates, a propensity score analysis was performed. Survival was estimated using the Kaplan-Meier method. Differences were considered significant with P-values <0.05. RESULTS: In the RT group, 45 patients (12.3%) had some type of graft reduction surgery: 31 (68.9%) patients had pulmonary lobectomies and 14 (31.1%) wedge resections. Of the total cohort, 30 patients (8.2%) were prioritized, 23% of whom required graft reduction surgery. The propensity score analysis matched 41 patients in each group. In the RT group, there was an increased need for cardiopulmonary bypass (P = 0.017) during surgery and extracorporeal membrane oxygenation (P = 0.025) after lung transplant. Furthermore, the median length of mechanical ventilation was higher (P = 0.008), and lung function at discharge, 3 and 6 months post-lung transplant was significantly lower in the RT group (P < 0.05). Survival analysis demonstrated a significantly poorer overall outcome at 1, 3 and 5 years post-lung transplantation in patients with a reduced graft (P = 0.007), while the 1-year conditional survival was also worse in this group (P = 0.025). CONCLUSIONS: Graft reduction surgery in lung transplant recipients is associated with lower pulmonary function and poorer overall survival. However, it does allow transplantation in prioritized recipients for whom it might otherwise be impossible to find an organ of suitable size.

Droughts and climate warming desynchronize Black pine growth across the Mediterranean Basin.

The effects of climate change on forest growth are not homogeneous across tree species distribution ranges because of inter-population variability and spatial heterogeneity. Although latitudinal and thermal gradients in growth patterns have been widely investigated, changes in these patterns along longitudinal gradients due to the different timing and severity of regional droughts are less studied. Here, we investigated these responses in Mediterranean Black pine (Pinus nigra Arn.). We built a tree-ring width dataset comprising 77 forests (1202 trees) across the Mediterranean Basin. The biogeographical patterns in growth patterns and the relationships between growth and mean temperature, precipitation, drought and atmospheric circulations patterns (NAO -North Atlantic Oscillation-, SOI -Southern Oscillation Index- and MOI -Mediterranean Oscillation index-) were analyzed. Then, we evaluated the spatial and temporal growth synchrony between and within east and west populations. We found different growth and climate patterns in west vs. east Black pine populations, although in both regions growth was driven by similar temperature and precipitation variables. MOI significantly influenced tree growth, whilst NAO and SOI showed weaker effects. Growth of east and west Black pine populations desynchronized after the 1970s when several and uncoupled regional droughts occurred across the Mediterranean Basin. We detected a climate shift from the 1970s to the 1980s affecting growth patterns, changing growth-climate relationships, and reducing forest growth from west to east Black pine forests. Afterwards, climate and growth of east and west populations became increasingly more divergent. Our findings imply that integral bioclimatic and biogeographical analyses across the species distribution area must be considered to adequately assess the impact of climate change on tree growth under warming and more arid conditions.

Pseudo skin flash on VMAT in breast radiotherapy: Optimization of virtual bolus thickness and HU values.

PURPOSE: Optimisation strategies for volumetric modulated arc therapy (VMAT) in most treatment planning systems for breast cancer do not account for patient positioning, breathing, or anatomical changes. To overcome this limitation, a pseudo-skin flash strategy using a virtual bolus has been proposed. Using this strategy, we determined optimal thickness and value of Hounsfield units (HU) assigned to the virtual bolus to ensure adequate CTV irradiation. MATERIALS AND METHODS: We modified the original computed tomography data (CT0) by adding combinations of thicknesses and densities of a virtual bolus on PTVs (CT') of seven bilateral breast cancer patients. Using a single optimization objective template, we obtained a VMAT plan on CT' and recalculated this on the CT0. Optimal CT' parameters were defined as those that minimized dose differences between CT' and CT0 plans regarding PTV and OAR dose-volume parameters. We studied bolus parameters regarding robustness by shifting the isocenter 5 and 10 mm in the breathing direction for each CT0 plan. RESULTS: The minimal dosimetric impact was between -400 and -600 HU depending on bolus thickness. OARs doses were not significantly affected. Best robustness was found for -500 HU and 15 mm bolus thickness against shifts of up to 10 mm in the breathing direction. CONCLUSION: Our results support a bolus thickness equal to the CTV-PTV margin plus 5 mm and a virtual bolus HU value around -500 and -400 depending on the bolus thickness chosen. These findings could play a useful role in maximisingrobustness and minimising the need for plan renormalization.

Regime shifts of Mediterranean forest carbon uptake and reduced resilience driven by multidecadal ocean surface temperatures.

The mechanisms translating global circulation changes into rapid abrupt shifts in forest carbon capture in semi-arid biomes remain poorly understood. Here, we report unprecedented multidecadal shifts in forest carbon uptake in semi-arid Mediterranean pine forests in Spain over 1950-2012. The averaged carbon sink reduction varies between 31% and 37%, and reaches values in the range of 50% in the most affected forest stands. Regime shifts in forest carbon uptake are associated with climatic early warning signals, decreased forest regional synchrony and reduced long-term carbon sink resilience. We identify the mechanisms linked to ocean multidecadal variability that shape regime shifts in carbon capture. First, we show that low-frequency variations of the surface temperature of the Atlantic Ocean induce shifts in the non-stationary effects of El Niño Southern Oscillation (ENSO) on regional forest carbon capture. Modelling evidence supports that the non-stationary effects of ENSO can be propagated from tropical areas to semi-arid Mediterranean biomes through atmospheric wave trains. Second, decadal changes in the Atlantic Multidecadal Oscillation (AMO) significantly alter sea-air heat exchanges, modifying in turn ocean vapour transport over land and land surface temperatures, and promoting sustained drought conditions in spring and summer that reduce forest carbon uptake. Third, we show that lagged effects of AMO on the winter North Atlantic Oscillation also contribute to the maintenance of long-term droughts. Finally, we show that the reported strong, negative effects of ocean surface temperature (AMO) on forest carbon uptake in the last decades are unprecedented over the last 150 years. Our results provide new, unreported explanations for carbon uptake shifts in these drought-prone forests and review the expected impacts of global warming on the profiled mechanisms.

Risky future for Mediterranean forests unless they undergo extreme carbon fertilization.

Forest performance is challenged by climate change but higher atmospheric [CO2 ] (ca ) could help trees mitigate the negative effect of enhanced water stress. Forest projections using data assimilation with mechanistic models are a valuable tool to assess forest performance. Firstly, we used dendrochronological data from 12 Mediterranean tree species (six conifers and six broadleaves) to calibrate a process-based vegetation model at 77 sites. Secondly, we conducted simulations of gross primary production (GPP) and radial growth using an ensemble of climate projections for the period 2010-2100 for the high-emission RCP8.5 and low-emission RCP2.6 scenarios. GPP and growth projections were simulated using climatic data from the two RCPs combined with (i) expected ca ; (ii) constant ca  = 390 ppm, to test a purely climate-driven performance excluding compensation from carbon fertilization. The model accurately mimicked the growth trends since the 1950s when, despite increasing ca , enhanced evaporative demands precluded a global net positive effect on growth. Modeled annual growth and GPP showed similar long-term trends. Under RCP2.6 (i.e., temperatures below +2 °C with respect to preindustrial values), the forests showed resistance to future climate (as expressed by non-negative trends in growth and GPP) except for some coniferous sites. Using exponentially growing ca and climate as from RCP8.5, carbon fertilization overrode the negative effect of the highly constraining climatic conditions under that scenario. This effect was particularly evident above 500 ppm (which is already over +2 °C), which seems unrealistic and likely reflects model miss-performance at high ca above the calibration range. Thus, forest projections under RCP8.5 preventing carbon fertilization displayed very negative forest performance at the regional scale. This suggests that most of western Mediterranean forests would successfully acclimate to the coldest climate change scenario but be vulnerable to a climate warmer than +2 °C unless the trees developed an exaggerated fertilization response to [CO2 ].

Oportunidade do uso da corticotomia alveolar associado ao tratamento da má oclusão de Classe II com aparelho Invisalign® – relato de caso / Class II malocclusion treatment option with alveolar corticotomy and Invisalign® appliance – case report

Corticotomia alveolar é uma das diferentes maneiras de acelerar e aumentar a eficiência do movimento dentário. O propósito desse trabalho é apresentar o planejamento e execução da fase acelerada do tratamento ortodôntico da má oclusão de Classe II com aparelho Invisalign® e auxílio de corticotomias alveolares.

Alveolar corticotomy is one of the different ways to accelerate and increase dental movement efficiency. The aim of this paper is to present the accelerated phase planning and implementation of a Class II malocclusion orthodontic treatment with Invisalign® appliance and the aid of alveolar corticotomies.

Experience in Bedside Placement, Clinical Validity, and Cost-Efficacy of a Self-Propelled Nasojejunal Feeding Tube.

BACKGROUND: The procedures needed to insert nasojejunal tubes (NJTs) are often invasive or uncomfortable for the patient and require hospital resources. The objectives of this study were to describe our experience in inserting a self-propelling NJT with distal pigtail end and evaluate clinical validity and cost efficacy of this enteral nutrition (EN) approach compared with parenteral nutrition (PN). MATERIALS AND METHODS: Prospective study from July 2009 to December 2010, including hospitalized noncritical patients who required short-term jejunal EN. The tubes were inserted at bedside, using intravenous erythromycin as a prokinetic drug. Positioning was considered correct when the distal end was beyond the ligament of Treitz. Migration failure was considered when the tube was not positioned into the jejunum within 48 hours postinsertion. RESULTS: Fifty-six insertions were recorded in 47 patients, most frequently in severe acute pancreatitis (69.6%). The migration rates at 18 and 48 hours postinsertion were 73.2% and 82.1%, respectively. There was migration failure in 8.9% of cases, and 8.9% were classified null (the tube was no longer in the gastrointestinal tract at 18 hours). There were no reported or observed complications. The mean duration of the EN was 12 ± 10.8 days. Five different types of EN formula were used. The total study cost was 53.9% lower compared with using PN in all patients. CONCLUSIONS: Our study demonstrated that bedside insertion of a self-propelling NJT is a safe, cost-effective, and successful technique for postpyloric enteral feeding in at least 73% of the patients, and only 18% of patients could eventually need other placement techniques. It can avoid the need for more aggressive or expensive placement techniques or even PN if we cannot achieve enteral access.

[Optimization of radiological scoliosis assessment]. / Optimización del estudio radiológico de la escoliosis.

Most scoliosis are idiopathic (80%) and occur more frequently in adolescent girls. Plain radiography is the imaging method of choice, both for the initial study and follow-up studies but has the disadvantage of using ionizing radiation. The breasts are exposed to x-ray along these repeated examinations. The authors present a range of recommendations in order to optimize radiographic exam technique for both conventional and digital x-ray settings to prevent unnecessary patients' radiation exposure and to reduce the risk of breast cancer in patients with scoliosis. With analogue systems, leaded breast protectors should always be used, and with any radiographic equipment, analog or digital radiography, the examination should be performed in postero-anterior projection and optimized low-dose techniques. The ALARA (as low as reasonable achievable) rule should always be followed to achieve diagnostic quality images with the lowest feasible dose.

Optimización del estudio radiológico de la escoliosis / Optimization of radiological scoliosis assessment

La mayoría de las escoliosis son idiopáticas (80%) y ocurren más frecuentemente en adolescentes y en el sexo femenino. La radiografía simple es el método de imagen de elección, tanto en el estudio inicial como en el seguimiento evolutivo, pero tiene el inconveniente de utilizar radiaciones ionizantes. Las mamas quedan en el campo de exposición durante estos estudios repetidos. Los autores presentan una serie de recomendaciones para optimizar la técnica de las exploraciones y los equipos radiográficos, tanto analógicos como digitales, para evitar dosis de irradiación innecesarias a los pacientes y reducir el riesgo de cáncer de mama en los pacientes con escoliosis. Cuando se utilizan equipos analógicos siempre debe utilizarse protector mamario plomado y, en todos los equipos, sean analógicos o digitales, hay que realizar la radiografía en proyección posteroanterior y con técnicas optimizadas de baja dosis. Hay que seguir siempre el principio ALARA (as low as reasonable achievable) para obtener imágenes diagnósticas de calidad con la dosis lo más baja posible (AU)

Most scoliosis are idiopathic (80%) and occur more frequently in adolescent girls. Plain radiography is the imaging method of choice, both for the initial study and follow-up studies but has the disadvantage of using ionizing radiation. The breasts are exposed to x-ray along these repeated examinations. The authors present a range of recommendations in order to optimize radiographic exam technique for both conventional and digital x-ray settings to prevent unnecessary patients' radiation exposure and to reduce the risk of breast cancer in patients with scoliosis. With analogue systems, leaded breast protectors should always be used, and with any radiographic equipment, analog or digital radiography, the examination should be performed in postero-anterior projection and optimized low-dose techniques. The ALARA (as low as reasonable achievable) rule should always be followed to achieve diagnostic quality images with the lowest feasible dose (AU)

3D DVH-based metric analysis versus per-beam planar analysis in IMRT pretreatment verification.

PURPOSE: To evaluate methods of pretreatment IMRT analysis, using real measurements performed with a commercial 2D detector array, for clinical relevance and accuracy by comparing clinical DVH parameters. METHODS: We divided the work into two parts. The first part consisted of six in-phantom tests aimed to study the sensitivity of the different analysis methods. Beam fluences, 3D dose distribution, and DVH of an unaltered original plan were compared to those of the delivered plan, in which an error had been intentionally introduced. The second part consisted of comparing gamma analysis with DVH metrics for 17 patient plans from various sites. Beam fluences were measured with the MapCHECK 2 detector, per-beam planar analysis was performed with the MapCHECK software, and 3D gamma analysis and the DVH evaluation were performed using 3DVH software. RESULTS: In a per-beam gamma analysis some of the tests yielded false positives or false negatives. However, the 3DVH software correctly described the DVH of the plan which included the error. The measured DVH from the plan with controlled error agreed with the planned DVH within 2% dose or 2% volume. We also found that a gamma criterion of 3%∕3 mm was too lax to detect some of the forced errors. Global analysis masked some problems, while local analysis magnified irrelevant errors at low doses. Small hotspots were missed for all metrics due to the spatial resolution of the detector panel. DVH analysis for patient plans revealed small differences between treatment plan calculations and 3DVH results, with the exception of very small volume structures such as the eyes and the lenses. Target coverage (D(98) and D(95)) of the measured plan was systematically lower than that predicted by the treatment planning system, while other DVH characteristics varied depending on the parameter and organ. CONCLUSIONS: We found no correlation between the gamma index and the clinical impact of a discrepancy for any of the gamma index evaluation possibilities (global, local, 2D, or 3D). Some of the tests yielded false positives or false negatives in a per-beam gamma analysis. However, they were correctly accounted for in a DVH analysis. We also showed that 3DVH software is reliable for our tests, and is a viable method for correlating planar discrepancies with clinical relevance by comparing the measured DVH of target and OAR's with clinical tolerance.

Radiation dose assessment in a 320-detector-row CT scanner used in cardiac imaging.

PURPOSE: In the present era of cone-beam CT scanners, the use of the standardized CTDI100 as a surrogate of the idealized CTDI is strongly discouraged and, consequently, so should be the use of the dose-length product (DLP) as an estimate of the total energy imparted to the patient. However, the DLP is still widely used as a reference quantity to normalize the effective dose for a given scan protocol mainly because the CTDI100 is an easy-to-measure quantity. The aim of this article is therefore to describe a method for radiation dose assessment in large cone-beam single axial scans, which leads to a straightforward estimation of the total energy imparted to the patient. The authors developed a method accessible to all medical physicists and easy to implement in clinical practice in an attempt to update the bridge between CT dosimetry and the estimation of the effective dose. METHODS: The authors used commercially available material and a simple mathematical model. The method described herein is based on the dosimetry paradigm introduced by the AAPM Task Group 111. It consists of measuring the dose profiles at the center and the periphery of a long body phantom with a commercial solid-state detector. A weighted dose profile is then calculated from these measurements. To calculate the CT dosimetric quantities analytically, a Gaussian function was fitted to the dose profile data. Furthermore, the Gaussian model has the power to condense the z-axis information of the dose profile in two parameters: The single-scan central dose, f(0), and the width of the profile, sigma. To check the energy dependence of the solid-state detector, the authors compared the dose profiles to measurements made with a small volume ion chamber. To validate the overall method, the authors compared the CTDI100 calculated analytically to the measurement made with a 100 mm pencil ion chamber. RESULTS: For the central and weighted dose profiles, the authors found a good agreement between the measured dose profile data and the fitted Gaussian functions. The solid-state detector had no energy dependence--within the energy range of interest--and the analytical model succeeded in reproducing the absolute dose values obtained with the pencil ion chamber. For the case of large cone-beam single axial scans, the quantity that better characterizes the total energy imparted to the patient is the weighted dose profile integral (DPI(w)). The DPI(w) can be easily determined from the two parameters that define the Gaussian functions: f(0) and sigma. The authors found that the DLP underestimated the total energy imparted to the patient by more than 20%. The authors also found that the calculated CT dosimetric quantities were higher than those displayed on the scanner console. CONCLUSIONS: The authors described and validated a method to assess radiation dose in large cone-beam single axial scans. This method offers a simple and more accurate estimation of the total energy imparted to the patient, thus offering the possibility to update the bridge between CT dosimetry and the estimation of the effective dose for cone-beam CT examinations in radiology, nuclear medicine, and radiation therapy.

Induction of incomplete and complex chromosome aberrations by 30 kVp X rays.

X rays of 26-30 kVp are routinely used for mammography screening. For radioprotection purposes, a quality factor (Q) of 1 is assumed for all photon energies, but it is thought that the relative biological effectiveness (RBE) increases as the photon energy decreases. The analysis of radiation-induced chromosome aberrations is one of the most widely used methods to study the interaction between radiation and DNA. Here we present a FISH study on metaphases from peripheral blood samples irradiated with three different X-ray energies (30, 80 and 120 kVp). The study comprises two FISH approaches: one using pantelomeric and pancentromeric probes to evaluate the induction of incomplete chromosome aberrations and the other using mFISH to evaluate the induction of complex chromosome aberrations. The results indicate that exposure to 30 kVp X rays resulted in a modest increase in the induction of incomplete elements and complex aberrations compared to 80 and 120 kVp X rays.

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers.

BRCA1 and BRCA2 genes are essential in preserving the integrity of genome, and it is not unambiguously clear whether the heterozygosity status may affect BRCA1 or BRCA2 functions. This may have implications for the clinical management of BRCA1 and BRCA2 mutation carriers both in breast cancer (BC) screening modality and in cancer treatment based on DNA-damaging or DNA-repair-inhibiting drugs. We investigated whether lymphocytes carrying BRCA1 or BRCA2 mutations displayed an increased sensitivity to radiation or mitomycin C (MMC) in vitro treatments. Peripheral blood from 21 BRCA1 mutation carriers (12 with BC and 9 healthy), 24 BRCA2 carriers (13 with BC and 11 healthy), 15 familial BC patients without detected mutation in BRCA1 or BRCA2 and 16 controls without familial history of cancer (5 with BC and 11 healthy) were irradiated or treated with MMC. Chromosomal damage was measured using the cytokinesis-block micronucleus assay. We evaluated micronuclei (MN) and nucleoplasmic bridges (NPBs). The BRCA2 mutation carriers and familial BC patients without detected mutation in BRCA1 or BRCA2 showed less basal NPB than BRCA1 carriers and controls. The BRCA1 (+/-) or BRCA2 (+/-) lymphocytes did not have increased frequencies of MN or NPB after irradiation. In contrast, BRCA2 (+/-) lymphocytes presented higher levels of MN after MMC exposure than BRCA1 carriers and controls. The monoallelic BRCA1 or BRCA2 pathogenic mutations seem not to be associated with an enhanced radiosensitivity. The mutation of one BRCA2 allele conferred an increased sensitivity to MMC, presumably because of the role of this gene in the repair of MMC-induced DNA damage. This finding indicates that the MMC-induced MN analysis could be useful in identifying functional deficiencies of BRCA2 or genes related to BRCA2. Since MMC can be used as an anti-cancer drug, these data may be relevant for the management and follow-up of BRCA2 mutation carriers.

Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint.

Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of gamma-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

Persistence of radiation-induced chromosome aberrations in a long-term cell culture.

The aim of the present study was to evaluate the persistence of chromosome aberrations induced by X rays. FISH painting and mFISH techniques were applied to long-term cultures of irradiated cells. With painting, at 2 Gy the frequency of apparently simple translocations remained almost invariable during all the culture, whereas at 4 Gy a rapid decline was observed between the first and the second samples, followed by a slight decrease until the end of the culture. Apparently simple dicentrics and complex aberrations disappeared after the first sample at 2 and 4 Gy. By mFISH, at 2 Gy the frequency of complete plus one-way translocations remained invariable between the first and last sample, but at 4 Gy a 60% decline was observed. True incomplete simple translocations disappeared at 2 and 4 Gy, indicating that incompleteness could be a factor to consider when the persistence of translocations is analyzed. The analysis by mFISH showed that the frequency of complex aberrations and their complexity increased with dose and tended to disappear in the last sample. Our results indicate that the influence of dose on the decrease in the frequency of simple translocations with time postirradiation cannot be fully explained by the disappearance of true incomplete translocations and complex aberrations. The chromosome involvement was random for radiation-induced exchange aberrations and non-random for total aberrations. Chromosome 7 showed the highest deviations from expected, being less and more involved than expected in the first and last samples, respectively. Some preferential chromosome-chromosome associations were observed, including a coincidence with a cluster from radiogenic chromosome aberrations described in other studies.

Mitotic delay in lymphocytes from BRCA1 heterozygotes unable to reduce the radiation-induced chromosomal damage.

Double strand breaks (DSB) are critical lesions involved in the formation of chromosomal aberrations. In response to DNA damage, the cell has mechanisms of repair and cell-cycle control to maintain the genome integrity in which BRCA1 gene is implicated. In the present study an evaluation of the radio-induced damage in G(2) phase of the cell cycle in lymphocytes from BRCA1 heterozygotes is presented. For this purpose Calyculin-A-based premature chromosome condensation (PCC) combined with mitotic arrest has been applied to examine with conventional cytogenetics the damage in G(2) and M phase cells, and to evaluate the G(2)-to-M phase transition. Irradiated peripheral blood lymphocytes from seven heterozygote females (BRCA1(+/-)) and seven control females (BRCA1(+/+)) have been analyzed. The mean proportion of G(2) cells in BRCA1(+/-) was significantly higher than in BRCA1(+/+), indicating a higher G(2) delay after IR exposure in cells from BRCA1(+/-) females. On the other hand, whereas the mean frequency of chromatid breaks (chtb) in G(2) cells was not statistically different between both groups, the mean frequency of chtb in M cells of the BRCA1(+/-) group was significantly higher than in the BRCA1(+/+) one. Moreover, the mean proportion of M cells with aberrations was significantly higher in BRCA1(+/-) than in BRCA1(+/+) suggesting that in spite of the higher G(2) delay of BRCA1(+/-) more damaged cells are able to pass the G(2)-to-M transition.

Cytogenetic damage induced by radiotherapy. Evaluation of protection by amifostine and analysis of chromosome aberrations persistence.

PURPOSE: To evaluate the cytogenetic damage induced by radiotherapy, the effect of concomitant amifostine and the persistence of translocations and dicentrics after the treatment. MATERIALS AND METHODS: Blood samples from 16 head and neck cancer patients were obtained at different times, just before treatment, at the 1st and 22nd sessions, at the end of radiotherapy, and one, four and 12 months later. Solid stain and fluorescent in situ hybridization (FISH) techniques were applied to analyse chromosome aberrations. RESULTS: In all the analysis the frequencies of dicentrics plus rings were slightly lower in the group of patients receiving concomitant amifostine, but in each sampling point the differences were not significant. The persistence of translocations and dicentrics one year after radiotherapy was very similar, with a decline of more than 50%. For all the chromosome aberrations considered, a negative correlation between their initial yield and the percentage of this yield remained 12 months after radiotherapy was observed (p < 0.05). CONCLUSION: No significant protection by amifostine against radiation-induced chromosome damage was observed in head and neck cancer patients treated only with radiotherapy. In these cases, the persistence of translocations and dicentrics during the first year after radiotherapy is similar and related to their initial yield.

Monte Carlo simulation of MOSFET detectors for high-energy photon beams using the PENELOPE code.

The aim of this work was the Monte Carlo (MC) simulation of the response of commercially available dosimeters based on metal oxide semiconductor field effect transistors (MOSFETs) for radiotherapeutic photon beams using the PENELOPE code. The studied Thomson&Nielsen TN-502-RD MOSFETs have a very small sensitive area of 0.04 mm(2) and a thickness of 0.5 microm which is placed on a flat kapton base and covered by a rounded layer of black epoxy resin. The influence of different metallic and Plastic water build-up caps, together with the orientation of the detector have been investigated for the specific application of MOSFET detectors for entrance in vivo dosimetry. Additionally, the energy dependence of MOSFET detectors for different high-energy photon beams (with energy >1.25 MeV) has been calculated. Calculations were carried out for simulated 6 MV and 18 MV x-ray beams generated by a Varian Clinac 1800 linear accelerator, a Co-60 photon beam from a Theratron 780 unit, and monoenergetic photon beams ranging from 2 MeV to 10 MeV. The results of the validation of the simulated photon beams show that the average difference between MC results and reference data is negligible, within 0.3%. MC simulated results of the effect of the build-up caps on the MOSFET response are in good agreement with experimental measurements, within the uncertainties. In particular, for the 18 MV photon beam the response of the detectors under a tungsten cap is 48% higher than for a 2 cm Plastic water cap and approximately 26% higher when a brass cap is used. This effect is demonstrated to be caused by positron production in the build-up caps of higher atomic number. This work also shows that the MOSFET detectors produce a higher signal when their rounded side is facing the beam (up to 6%) and that there is a significant variation (up to 50%) in the response of the MOSFET for photon energies in the studied energy range. All the results have shown that the PENELOPE code system can successfully reproduce the response of a detector with such a small active area.

Repair of DNA broken ends is similar in embryonic fibroblasts with and without telomerase.

Telomeres cap the ends of chromosomes, preventing end-to-end fusions and subsequent chromosome instability. Here we used a telomerase knockout model to investigate whether telomerase participates in the processes of DNA break repair by de novo synthesis of telomere repeats at broken chromosome ends (chromosome healing). Chromosome healing giving rise to new detectable telomeric signals has not been observed in embryonic fibroblasts of telomerase-proficient mice exposed to ionizing radiation. Since the synthesis of telomeric sequences to broken DNA ends would make them refractory to rejoining events, the efficiency of rejoining of broken chromosomes in cell environments with and without telomerase has also been investigated. We conclude that the efficiency of rejoining broken chromosomes is not significantly different in the two cell environments. All together, our results indicate that there is no significant involvement of telomerase in the healing of broken DNA ends by synthesizing new telomeres in mouse embryo fibroblasts after exposure to ionizing radiation.