Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy:A Case-Control Study

Background: Previous studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied. Materials and Methods: We conducted a nested case-control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation. Results: The study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61-1.46 Gy) vs. (0.49-1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35). Conclusion: Despite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic

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Short-term accumulation and elimination of carbon-14 in the common carp Cyprinus carpio under laboratory conditions

International audienceThis study examined the short term transfer of carbon-14 (14C) in the common carp Cyprinus carpio under laboratory conditions. Various experiments were achieved in order to investigate direct or trophic transfer for 4 days, using waterborne 14C-labelled arginine or 14C-labelled food pellets respectively. Radiolabelled food was prepared with 14C-labelled arginine or glucose in order to test how transfer kinetics might vary with the biochemical form of 14C. Elimination experiments were achieved using fish fed for 5 days on radiolabelled food and then placed under starvation for 4 days. In all experiments, water, food and fish activities were monitored every day. Different fish fractions (whole body, muscle) were sampled in order to elucidate the role of muscle as a potential storage. Results suggested that direct water-to-fish absorption rate was 20% d-1 per fish. Carps incorporated 14.3% of the absorbed 14C. Fish activity did not increase over days, due to a strong decrease in 14C concentration in the water (resulting from aquarium sorption). During trophic transfer experiments, food was entirely ingested and 14C sources rapidly assimilated. For either arginine or glucose, results suggested that 19-20% of ingested 14C was incorporated, yielding a significant increase in fish activity over days. No difference in mass-specific activity was observed among muscle and whole body. Total activity in the muscle represented 29%-32% of whole body activity, this proportion reflecting the contribution of muscle to whole body weight. During elimination experiments, results showed a significant decrease in whole body total activity and mass-specific activity with arginine. The decrease was not significant with glucose due to a great variability among fish. Results suggested that an essential amino-acid like arginine can be used as an energy source under starvation and that muscles can act as a storage for essential amino-acids

Use of combined microscopic and spectroscopic techniques to reveal interactions between uranium and Microbacterium sp. A9, a strain isolated from the Chernobyl exclusion zone

Although uranium (U) is naturally found in the environment, soil remediation programs will become increasingly important in light of certain human activities. This work aimed to identify U(VI) detoxification mechanisms employed by a bacteria strain isolated from a Chernobyl soil sample, and to distinguish its active from passive mechanisms of interaction. The ability of the Microbacterium sp. A9 strain to remove U(VI) from aqueous solutions at 4 °C and 25 °C was evaluated, as well as its survival capacity upon U(VI) exposure. The subcellular localisation of U was determined by TEM/EDX microscopy, while functional groups involved in the interaction with U were further evaluated by FTIR; finally, the speciation of U was analysed by TRLFS. We have revealed, for the first time, an active mechanism promoting metal efflux from the cells, during the early steps following U(VI) exposure at 25 °C. The Microbacterium sp. A9 strain also stores U intracellularly, as needle-like structures that have been identified as an autunite group mineral. Taken together, our results demonstrate that this strain exhibits a high U(VI) tolerance based on multiple detoxification mechanisms. These findings support the potential role of the genus Microbacterium in the remediation of aqueous environments contaminated with U(VI) under aerobic conditions

Influence of root exudation of white lupine (Lupinus albus L.) on uranium phytoavailability in a naturally uranium-rich soil

International audienceMechanisms of uranium (U) transfer from soil to plants remain poorly understood. The kinetics of supply of U to the soil solution from solid phases could be a key point to understand its phytoavailability and implications for environmental risk assessment. Root activity, particularly the continuous release of organic acids in the rhizosphere, could have an effect on this supply. We tested the impact of citrate exudation by roots of Lupinus albus, either P-sufficient (P+) or P-deficient (P-), on the phytoavailability of U from a naturally contaminated soil (total content of 413 mg U kg−1) using a rhizotest design. Combined effects of P (P-/P+ used to modulate plant physiology) and citrate (model exudate) on the solubilization of U contained in the soils were tested in closed reactors (batch). The batch experiment showed the existence of a low U available pool (0.4% total U) and high accessibility (kd’ around 20 L kg−1) which was not significantly affected by P treatment or citrate concentrations. Analysis of U, Fe, Ca, P and citrate concentrations in the batches suggested a complex combination of mechanisms and factors including desorption, resorption, precipitation, co-sorption. On rhizotest, L. albus plants extracted 0.5–0.75% of the total U and between 25 and 40% of the estimated available U present in the rhizotest in 5 days. Uranium accumulation at the whole plant level (20 mg U kg−1d.w., shoot to root ratio around 10−3) seemed to be dependent neither on the plant P nutrition status nor citrate exudation level, possibly in relation with the equivalent accessibility of U whatever the growth conditions. Yet differential translocation to shoots seemed to be positively correlated to citrate exudation

Behavior of steroids and veterinary antibiotics in soil: study of transfer and degradation in soil columns.

communication par afficheInternational audienceAntibiotics are more and more used for animal treatments and are excreted unchanged. So, these compounds can enter the environment through land application of manure. This phenomenon could induce a resistance to antibiotics in human or animal medicine. Steroids, which are endocrine disruptors are also found in the environment due to animals but also humans wastes. The presence, distribution, fate and impact of veterinary substances and hormones regularly introduced into the soil via land application are far from known and very poorly characterised at the present time. In this context, the project aims at the development of methodologies based on soil columns experiments, in order to characterise the main products of biotic and abiotic transformations and to evaluate the migration and/or retention of selected contaminants and their breakdown products. For this purpose, 45 substances were selected including 11 hormonal steroids, 23 veterinary compounds and 11 other well-known human contaminants. The surface of the columns were first spiked with the different compounds and then regularly watered with artificial rain (0.01 M CaCl2 in distilled water). The leachates were regularly collected and analysed using a multi-residue method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several series of columns were set up for periods ranging between 0 and 30 days. After this, the columns were sectioned into 5 horizons that were analysed using an original method based on a sample extraction by QuEChERS followed by a purification by solid phase extraction and an analysis by LC-MS/MS. Then, the presence and distribution of contaminants in the different horizons and/or leachates were established. The influence of various parameters on this transfer was also examined such as the pluviometry and the composition of soil (clay, loam, sand and organic matter contents)

Multigenerational exposure to gamma radiation affects offspring differently over generations in Zebrafish

International audienceMutigenerational studies have become of great interest in ecotoxicology and previously provided original results on the effects of offspring irradiation in model fish Danio rerio. Here, the irradiation of zebrafish was maintained until F2 larval stage. Two dose rates were selected; the first one (0.05 mGy h-1) was close to the threshold value for the protection of aquatic ecosystems, the second one (5 mGy h-1) previously studied and known to increase morbidity (DCRL). F1 from 30d-irradiated parents were irradiated themselves (irradiated condition) or not (Recovery condition) for 131 days before reproduction. Endpoints concerned reproductive capacity (reproductive success, fecundity, egg fertilization) and larval survival in F0, F1 and F2. Multigenerational irradiation affected F1 parental reproductive capacity mainly over the first reproduction and larval survival rate. Unexpected effects on sex ratio was observed in exposed and non-exposed F1 progeny after parental irradiation (mainly at 5 mGy h-1). The worsening effects over the two generations observed here could partly explain the higher sensitivity of wild populations. Thus, this study confirm that multigenerational studies could be of interest on ecological risk assessment, in particular to determine the benchmark values

Two distinct mechanisms lead to either oocyte or spermatocyte decrease in C. elegans after whole developmental exposure to γ-rays

International audienceWildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend speciesspecific differences in radiosensitivity. From our previous studies, we found that decrease in reproduction is life stage dependent in the roundworm Caenorhabditis elegans, possibly resulting from an accumulation of damages during germ cell development and gamete differentiation. To go further, we used the same experimental design to assess more precisely the molecular determinants of reproductive toxicity, primarily decreases in gamete number. As before, worms were chronically exposed to 50 mGyh-1 external gamma ionizing radiation throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). To enable cross species extrapolation, conserved molecular pathways across invertebrates and vertebrates were analysed: apoptosis and MAP kinase Ras/ ERK (MPK-1), both involved in reproduction and stress responses. Our results showed that these pathways are life-stage dependent, resulting from an accumulation of damages upon chronic exposure to IR throughout the life development. The Ras/ERK pathway was activated in our conditions in the pachytene region of the gonad where it regulates cell fate including apoptosis, but not in the ovulation zone, where it controls oocyte maturation and ovulation. Additionally, assessment of germ cell proliferation via Ras/ERK pathway showed no effect. Finally, a functional analysis of apoptosis revealed that while the decrease of the ovulation rate is caused by DNA-damaged induced apoptosis, this process does not occur in spermatocytes. Thus, sperm decrease seems to be mediated via another mechanism, probably a decrease in germ cell proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure. These results are of main importanc

Uptake and translocation of cesium by Arabidopsis thaliana in hydroponics conditions: Links between kinetics and molecular mechanisms

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Tritiated thymidine induces developmental delay, oxidative stress and gene overexpression in developing zebrafish (Danio rerio)

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