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Contribution à l'évaluation du risque pour l'homme lors de l'apparition de neurotoxines émergentes : analyse de réponses cellulaires et sélection de modèles expérimentaux de criblage.

Abstract : Phytoplanktonic toxins present a wide diversity of chemical structures and biological effects. The increasing number of families of toxins as well as the frequency of unexplained toxic periods makes the in vivo assays difficult to interpret. As a consequence, complementary methods such as chemical analyses have been developed, and allow the specific detection of known toxins for regulatory purposes. But, it is important to be able to detect new toxins or new analogs of known toxins in order to protect human health. Therefore, new approaches have to be implemented to (i) contribute to a better assessment of the risk related to emerging toxins and (ii) to improve knowledge on toxic periods. One of the approaches relies on the development of cellular models sensitive to different types of toxicities in order to use them when unknown toxicity occurs. This work is a contribution to the risk assessment related to unknown toxins, based on the analysis of cellular responses when cells are exposed to neurotoxic toxins. The cell line Neuro-2a was selected as a model for the study of cellular responses to different neurotoxins for which knowledge on the modes of action differ. The first part of the work was to characterize the responses of this model exposed to saxitoxins, neurotoxins acting the site 1 of the voltage-gated sodium channel. This approach has allowed the first description of saxitoxins in French freshwaters and to discuss the risk for human health. We next investigate the responses of the Neuro-2a model exposed to palytoxin and analogs which are emerging neurotoxins targeting the Na+, K+-ATPase pump. Finally, the cellular effects of 13-desmethyl-C spirolide, an emerging neurotoxin for which few toxicological studies are available, were investigated. As a discussion, the whole data obtained are replaced in a more general context dealing with the use of cellular models to contribute to a better understanding of phytoplanktonic toxic periods and the risk they may represent for human.
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https://pastel.archives-ouvertes.fr/pastel-00594239
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Submitted on : Thursday, May 19, 2011 - 12:01:20 PM
Last modification on : Monday, October 19, 2020 - 11:02:11 AM
Long-term archiving on: : Saturday, August 20, 2011 - 2:25:55 AM

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  • HAL Id : pastel-00594239, version 1

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Aurélie Ledreux. Contribution à l'évaluation du risque pour l'homme lors de l'apparition de neurotoxines émergentes : analyse de réponses cellulaires et sélection de modèles expérimentaux de criblage.. Ecotoxicologie. AgroParisTech, 2010. Français. ⟨NNT : 2010AGPT0024⟩. ⟨pastel-00594239⟩

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