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Intérêt des lignées cellulaires de poisson en écotoxicologie pour l'étude de nouveaux biomarqueurs de génotoxicité

Abstract : In a context of growing awareness of aquatic pollution impacts, there is an increasing need to develop methods for hazards and risk assessment of pollutants. In this context, genotoxicity endpoints are of a great concern since even when evaluated at a sub-cellular or cellular level, impaired DNA structure, repair and/or functions can have delayed (long term) consequences at higher level of organization such as individual and population. Some genotoxicant can have direct effect on DNA, but they can also interact indirectly, by modulating the repair mechanism efficiency or by acting on epigenetic mechanism such as DNA méthylation level. An unrepaired DNA damage and epigenetic modification can both lead to functional alteration and/or genetic structure at the population level. However, most of the existing genotoxicity test only measure primary DNA damage induces by genotoxicant; thus there is a real need to develop new tools to investigate those different kinds of genotoxicity. For this purpose, this work aims at developing knowledge in DNA repair capacities of to fish cell lines, RTL-W1 and RTG-W1, in order to develop new genotoxicity biomarker, measuring primary DNA damage by means of modified version of the comet assay. The results highlights the interest of in vitro biological models such as fish cell lines for the assessment of environmental genotoxicity, especially using a Fpg-modified comet assay allowing a sufficient increase of the assay sensibility to detect genotoxicity at environmentally relevant concentration. Results also characterize BER and PER capacities as being efficient repair mechanism in those fish cell lines, whereas NER, although also present, seems less efficient. A new biomarker based on the BER incision capacities of cellular extracts has also been developed and used to assess the genotoxicity of environemental effluent.
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Submitted on : Thursday, February 27, 2014 - 4:52:08 PM
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  • HAL Id : tel-00952888, version 1

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Aude Kienzler. Intérêt des lignées cellulaires de poisson en écotoxicologie pour l'étude de nouveaux biomarqueurs de génotoxicité. Sciences agricoles. INSA de Lyon, 2013. Français. ⟨NNT : 2013ISAL0016⟩. ⟨tel-00952888⟩

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