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Signatures moléculaires impliquées dans la transformation des cellules Bhas 42 induite par les silices amorphes synthétiques

Abstract : Synthetic amorphous silica nanoparticles (SAS) are used in many industrial applications. Due to their amorphous structure, SAS are not considered carcinogenic in humans, unlike silica with crystalline structures. However, in vivo and in vitro studies have proposed that certain SAS could potentially be carcinogenic. The Bhas 42 cell transformation test was developed to assess the transforming effects of chemical agents. A study carried out at the INRS highlighted the capacity of the precipitated SAS NM-200 and NM-201 and the pyrogenic SAS NM-202 and NM-203 to induce cell transformation. In order to study the molecular effects induced by SAS which lead to the transformation of Bhas 42 cells, we performed an unsupervised transcriptomic analysis, after exposure of Bhas 42 cells to SAS NM-203, and to reference chemical agents, crystalline silica Min-U-Sil 5® used as a positive particulate control, diatomaceous earth (DE), an amorphous silica microparticle used as a negative particulate control and 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter. The results show a link between the transformation of Bhas 42 cells induced by pyrogenic SAS NM-203, crystalline silica Min-U-Sil 5® and TPA and the modification of the expression of genes and signaling pathways involved in proliferation, cell adhesion, DNA repair and inflammation. In addition, we have identified a common signature of 21 genes involved in the early stages of cell transformation induced by the three chemical agents. The genes composing the common signature are involved in cell proliferation and adhesion. Among them, 12 genes were selected according to their expression level (over-expressed or under-expressed) 48 hours after treatment with chemical agents. Similar gene alterations have also been obtained when Bhas 42 cells are treated with NM-200 precipitated SAS and NM-202 pyrogenic. In conclusion, this work highlights a link between the formation of transformation foci induced by the treatment of Bhas 42 cells with SAS, crystalline silica Min-U-Sil 5® and TPA and changes in expression profiles of genes and signaling pathways. The signature of the 12 genes represents a list of potential and common "biomarkers" of cell transformation induced by SAS, crystalline silica Min-U-Sil 5® and TPA.
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Submitted on : Monday, June 22, 2020 - 2:18:27 PM
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  • HAL Id : tel-02877489, version 1

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Anaïs Kirsch. Signatures moléculaires impliquées dans la transformation des cellules Bhas 42 induite par les silices amorphes synthétiques. Sciences du Vivant [q-bio]. Université de Lorraine, 2020. Français. ⟨NNT : 2020LORR0015⟩. ⟨tel-02877489⟩

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