13 research outputs found

    Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

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    International audiencePolycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (gammaH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment

    Stability Assessments on Luminescent Down-Shifting Molecules for UV-Protection of Perovskite Solar Cells

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    International audienceIn this work the use of a S-tetrazine (NITZ) molecule with down-shifting capability to improve the stability of perovskite solar cells is reported. Indeed perovskite solar cells are known to present a high sensitivity to UV light and one strategy to overcome this issue is to actually supress the UV from the illumination light. The NITZ down-shifting molecule is well suited for this application since it has the particularity to be excited in the near-UV region and to emit into the visible light spectrum, giving the possibility to recycle UV photons for additional current generation. Through current-voltage curves, incident-photon-to-electron conversion efficiency, and photoluminescence spectroscopy characterization we show that NITZ presents an emission quantum yield of 30% which allows to reduce the loss of J SC induced by the use of a conventional UV filter, even if a net gain in photocurrent is not achieved in our case. We also present a simple prediction of the ability of a down-shifting molecule to efficiently perform for a specific active material. Moreover, we finally discuss the possibility to improve using such down-shifting strategy, the performance of some perovskite solar cells based on alternatives electron-transporting layers such as WO3, which are known to alter the active layer performance following UV light absorption

    Comparative genotoxic potential of 27 polycyclic aromatic hydrocarbons in three human cell lines

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    International audiencePolycyclic Aromatic Hydrocarbons (PAHs) form a family of compounds that are generally found in complex mixtures. PAHs can lead to the development of carcinogenesis. The Toxicity Equivalent Factor (TEF) approach has been suggested for estimating the toxicity of PAHs, however, due to the relative weakness of available data, TEF have not been applied for the risk characterization of PAHs as food contaminants in Europe. The determination of new TEFs for a large number of PAHs could overcome some limitations of the current method and improve cancer risk assessment. The present investigation aimed at deriving new TEFs for PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a genotoxicity assay (gamma H2AX) with three human cell lines to analyze the genotoxic properties of 27 selected PAHs after 24 h treatment. For 11 compounds, we did not detect any genotoxic potential. For the remaining 16 PAHs, the concentration-response for genotoxic effect was modelled with the Hill equation; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. We developed for each compound, in each cell line, Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were similar in all cell lines and generally higher than the TEF usually used. These new equivalent factors for PAHs should improve cancer risk assessment

    Genotoxic effect of polycyclic aromatic hydrocarbons alone or in mixture

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    Polycyclic Aromatic Hydrocarbons (PAHs) are a family of more than one hundred compounds and are potentially carcinogenic to humans. Hazard characterization of PAH complex mixtures is currently based on Toxicity Equivalent Factors (TEFs). However, this method present some limits and it is relevant to define new TEFs for a large number of PAH in order to improve cancer risk assessment for humans. In this study, we used a new genotoxic assay (based on gH2AX quantification) to analyze the genotoxicity of 27 PAHs on three human cell lines representative of major target organs of PAHs: liver (Hep3B), colon (LS-174T) and lung (NCI-H358). Mathematical models were used to determine new TEFs values for PAHs. Dose-genotoxic response modelling was performed using a Hill model, with a focus on effects equivalency between PAHs at low dose. We observed a significant dose-response of genotoxicity in the three cell lines tested for 16 tested compounds and developed new TEFs that we named GEF for Genotoxic Equivalent Factor. Calculated GEFs for the tested PAHs were generally higher than usually utilized TEFs. We further explored the effect of PAH mixtures by testing 16 binary mixtures on LS-174T cells. In some cases, antagonistic, potentiation or synergic actions, or a variation of the maximum response were observed in relation to concentration addition. To confirm these interactions, DNA adducts quantification and metabolic studies are under investigation. Finally, more complex mixtures of PAHs based on 4, 8 or 16 compounds were tested and the genotoxic effect of these mixtures was predicted with concentration addition. In this study, we proposed new TEFs for PAHs based on their genotoxic effects on human cells investigated at low doses. Moreover, we developed mathematical models to predict PAH mixtures genotoxic effect. This method will be useful to improve cancer risk assessment for humans exposed to PAHs

    Search for potassium transport systems involved in arbuscular mycorrhiza-rice symbiotic interactions

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    International audienceArbuscular mycorrhizal fungi (AMF) develop interdependent connections with roots of about90% of plant species. These interactions increase availability as well as translocation ofnutrients (especially N and P), and thereby improve plant nutrition and growth. Moreover,resistance to a variety of stresses, among which salt stress, has been shown to be improved byAMF-plant interactions, for example in rice. Intense research to explain the molecularmechanisms of AMF-plant beneficial interactions led to the identification of phosphate andammonium transporters involved in nutrient exchanges from AMF to the plant, in several plantspecies. In spite of the importance of potassium (K+) for plant physiology, the contribution ofAMF symbiosis to plant K+ nutrition has been little documented. Over-expression of plant K+transporters has been described in Lotus japonicus and tomato in condition of AMF symbiosis.Furthermore, K+ transport systems in the AMF Rhizophagus irregularis have been identified insilico. Here, K+ nutrition in rice colonized by R. irregularis has been analyzed at molecular andphysiological levels. Surprisingly, major K+ transport systems in rice were down-regulated uponAMF interactions, suggesting strong increase in K+ availability for uptake by root cells insymbiotic conditions. Role of K+ in the relationships between rice and R. irregularis will also bediscusse

    Recherche de systèmes de transport de potassium impliqués dans le transfert de K+ de la mycorhize arbusculaire au riz lors d'interactions symbiotiques

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    National audienceLes champignons mycorhiziens à arbuscules (CMA) développent des connexions interdépendantes avec les racines d'environ 90% des espèces végétales. Ces interactions augmentent la disponibilité ainsi que la translocation des nutriments (en particulier N et P), et améliorent ainsi la nutrition et la croissance des plantes. De plus, la résistance à une variété de stress, parmi lesquels le stress salin, s'est avérée améliorée par les interactions CMA-plante, par exemple chez le riz. Des recherches intenses pour expliquer les mécanismes moléculaires des interactions bénéfiques CMA-plante ont conduit à l'identification de transporteurs de phosphate et d'ammonium impliqués dans les échanges de nutriments du CMA vers la plante, chez plusieurs espèces végétales. Malgré l'importance du potassium (K+) pour la physiologie des plantes, la contribution de la symbiose mycorhizienne à arbuscule à la nutrition en K+ des plantes a été peu documentée. La surexpression des transporteurs de K+ végétaux a été décrite chez Lotus japonicus et la tomate en condition de symbiose mycorhizienne à arbuscule. Ici, la nutrition en K+ du riz colonisé par Rhizophagus irregulis a été analysée aux niveaux moléculaire et physiologique. Étonnamment, les principaux systèmes de transport de K+ dans le riz étaient régulés à la baisse lors des interactions AMF, suggérant une forte augmentation de la disponibilité de K+ pour l'absorption par les cellules racinaires dans des conditions symbiotiques. De plus, des systèmes de transport de K+ dans le CMA R. irregularis ont été identifiés in silico. La fonction de l’un d’entre eux a été analysée. Le rôle de K+ dans les relations entre le riz et R. irregularis sera également discuté

    Stress signalling dynamics of the mitochondrial electron transport chain and oxidative phosphorylation system in higher plants

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    International audienceBackground - Mitochondria play a diversity of physiological and metabolic roles under conditions of abiotic or biotic stress. They may be directly subjected to physico-chemical constraints, and they are also involved in integrative responses to environmental stresses through their central position in cell nutrition, respiration, energy balance and biosyntheses. In plant cells, mitochondria present various biochemical peculiarities, such as cyanide-insensitive alternative respiration, and, besides integration with ubiquitous eukaryotic compartments, their functioning must be coupled with plastid functioning. Moreover, given the sessile lifestyle of plants, their relative lack of protective barriers and present threats of climate change, the plant cell is an attractive model to understand the mechanisms of stress/organelle/cell integration in the context of environmental stress responses. Scope - The involvement of mitochondria in this integration entails a complex network of signalling, which has not been fully elucidated, because of the great diversity of mitochondrial constituents (metabolites, reactive molecular species and structural and regulatory biomolecules) that are linked to stress signalling pathways. The present review analyses the complexity of stress signalling connexions that are related to the mitochondrial electron transport chain and oxidative phosphorylation system, and how they can be involved in stress perception and transduction, signal amplification or cell stress response modulation. Conclusions - Plant mitochondria are endowed with a diversity of multi-directional hubs of stress signalling that lead to regulatory loops and regulatory rheostats, whose functioning can amplify and diversify some signals or, conversely, dampen and reduce other signals. Involvement in a wide range of abiotic and biotic responses also implies that mitochondrial stress signalling could result in synergistic or conflicting outcomes during acclimation to multiple and complex stresses, such as those arising from climate change
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