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Inhibition de l'apoptose comme facteur de la transformation morphologique des cellules embryonnaires de hamster Syrien

Abstract : Apoptosis, a cell suicide pathway, is implicated in various physiological events, in particular the elimination of damaged cells. The defective regulation of apoptosis may contribute to the etiology of cancer and the impairment of normal cell death process has been implicated in neoplastic transformation. In order to test the hypothesis of a relationship between apoptosis and neoplastic transformation, we studied three chemicals, zinc as inhibitor of apoptosis, DEHP (di-2-ethylhexyl phtalate) which induced cell transformation and 2,4-D (2,4-dichlorodiphénoxyacetic acid), a peroxysome proliferators such DEHP. First, we demonstrated that anti-apoptotic chemicals (zinc and DEHP) induced SHE cell transformation. These results were in agreement with the theory of a relationship between the inhibition of apoptosis and the induction of cell transformation. However, 2,4-D induced SHE cell transformation while it has no effect on apoptosis. Second, we showed that zinc and DEHP inhibited apoptosis through an increase of the bcl-2/bax ratio. Results concerning the involvement of the proto-oncogene c-myc in apoptosis and in cell transformation are more complex. We showed that 2,4-D induced c-myc expression at concentrations which induced cell transformation. On the opposite, DEHP decreased c-myc expression which could be related to the increase of the Bcl-2 expression.
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Marie-Aline Maire. Inhibition de l'apoptose comme facteur de la transformation morphologique des cellules embryonnaires de hamster Syrien. Toxicologie. Université Paul Verlaine - Metz, 2004. Français. ⟨NNT : 2004METZ034S⟩. ⟨tel-01750008⟩

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