. .. Extractions-protéiques,

, Dosage de la périostine par enzyme-linked immuno assay

, Analyse par microscopie électronique à transmission

. .. Analyse-statistique,

I. V. Chapitre, . .. Resultats, and T. .. De, 54 1. Résultats initiaux et hypothèse de travail, des cellules Bhas 42 induite par un traitement unique avec les SAS précipitées NM-200, vol.57

. .. Pca),

, Regroupement hiérarchique non supervisé des données

, Effet moléculaire induit par la SAS pyrogénée NM-203

. .. Gsea), Comparaison des signatures moléculaires obtenues avec des données de la littérature

, 3.4. Réseaux de gènes impactés par la SAS pyrogénée NM-203, La SAS pyrogénée NM-203 induit une modification de voies de signalisation liées au cycle cellulaire et à la réparation de l'ADN

, Analyse DAVID et Panther), La SAS pyrogénée NM-203 induit une modification de voies de signalisation liées à l'inflammation et à l'adhésion cellulaire

. .. Tpa, 74 6.4.1 Comparaison des signatures moléculaires obtenues avec des données de la littérature (GSEA), Comparaison des signatures moléculaires induites par la SAS pyrogénée NM-203 avec la silice cristalline Min-U-Sil 5

. .. Tpa, La SAS pyrogénée NM-203 induit une modification de voies de signalisation communes à la silice cristalline Min-U-Sil 5

. .. , 82 6.5.1 Signature commune de la transformation cellulaire, Comparaison des signatures moléculaires et sélection des gènes communs

, Validation des résultats de transcriptomique par RT-qPCR, vol.87

, Validité de la signature commune pour d'autres SAS, vol.87

, Cinétique

, Étude de la corrélation entre ARNm et protéines

V. Chapitre and . .. Discussion,

, Tests de transformation et approche transcriptomique

S. Les and .. .. ,

, Signatures moléculaires induites et voies de signalisation modifiées par la SAS pyrogénée NM-203

. .. ,

, Avantages et limites de l'utilisation du test de transformation et du modele Bhas 42

V. I. Chapitre, . Conclusion, and . .. Perspectives,

V. Chapitre and . .. References,

V. Chapitre and . .. Annexes,

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, supplemented with 1% (v/v) antibiotic (Streptomycin and Penicillin, Gibco?) and 10% (v/v) fetal bovine serum (FBS, Dutscher, Bhas 42 cells were obtained from Harlan Laboratories, p.10

, Cell transformation and cell survival assays The CTA in promotion condition, originally proposed by the OECD

, Supplementary Table A2). Amplification was performed following the manufacturer

, TUBA (alpha-Tubulin), and GAPDH (glyat 4°C. Supernatants were collected and stored at ?80°C. Protein concentration was measured in each sample and corresponding cell medium supernatant, using bovine serum albumin as a standard, ACTB (beta-Actin)

, ?g) of whole cell homogenates or 20 ?l of corresponding cell medium supernatants were resolved in 4-20% SDS PAGE (CriterionTM Tris-Glycine eXtended Stain-Free Protein Gel, BioRad) and transferred onto polyvinylidene difluoride (PVDF) membranes (BioRad), using semi-dry transfert (BioRad). and Ninein interacting protein (AUNIP, 500), Galectin-7, vol.1, p.1000, 206435.

, Mini Chromosome Maintenance deficient 10 (MCM10, vol.1, p.1000

?. , Gene clustering was visualized with Treeview. An uncentred correlation was used as a measure of similarity and complete linkage was used for the clustering method. (B) Dose effect of NM-203 (1-5 ?g/cm 2 ). Supervised hierarchical clustering was performed with Gene Cluster 3.0 software and visualized by Treeview on the 285 probes obtained after filtration and application of the ANOVA statistical test, Min-U-Sil 5® (20 ?g/cm 2 ), vol.1, pp.0-203

, TPA, 12-O-tetradecanoylphorbol-13-acetate

D. De and . Earth,

. Dmso, 5000) or HRP-conjugated anti-rabbit IgG (1: 2000) in PBST containing 5% (w/v) non-fat milk. Finally, membranes were washed 3 times with PBST before chemiluminescence detection (Clarity ? Western ECL Substrate, BioRad) using ChemiDocTM (ChemiDoc ? System, BioRad), For interpretation of the references to color in HRP-conjugated anti-goat IgG

. Graphpad,

, An unpaired t-test was used for two by two comparison (treatments vs. control (H 2 O or DMSO)). Data are given as a mean ± standard deviation (mean ± SD)

, Gene set enrichment analysis. (A) GSEA analysis using the filtered gene expression profiles of Bhas 42 cells 48 h after treatment with NM-203 (5 ?g/cm 2 ), Min-U-Sil 5® (20 ?g/cm 2 ) and TPA

, List of the 12 common signatures. (C) GSEA revealed an enrichment in gene signatures related to cell cycles and cancer, ?g/ml) over 48 h. Venn diagram of the top 50 signatures. (B)

A. Kirsch, Chemico-Biological Interactions, vol.315, p.108900, 2020.

, Genes significantly highly regulated by NM-203 (5 ?g/cm 2 ), Min-U

C. Cacna1g, . Lum, . Postn, . Sema3g, T. Sparcl1 et al., Of the 309 genes altered by treatments, a large majority (83%) were affected by NM-203. Among these, 142 (46%) were affected solely by NM-203 treatment and 23 (7%) and 29 genes (9%) were deregulated by Min-U-Sil 5® and TPA, respectively. Interestingly, 21 common genes were regulated significantly by NM-203 (5 ?g/cm 2 ), Min-U-Sil 5® and TPA (p < 0.005, FC > 4). Twelve genes, Sil 5® and TPA were compared (p < 0.005 and FC > 4) (Fig. 4A)

. Lum, . Postn, and S. Sema3g, Transforming silica nanoparticles NM-200 and NM-202 induce similar changes at the RNA level of the selected genes We then assessed whether Bhas 42 cell exposure to other SAS, namely NM-200, NM 201 and NM202, led to cell transformation and involved any changes at the RNA level of the selected genes, NM-200 of AUNIP, IL1RL1, MCM10, PRL2C1, PRL2C3 and PRL2C5, and a decrease for LGALS7

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. Sas-nm-,

S. Sas-nm-202 and . De-or-min, U-Sil 5 Ò , and with DMSO as the vehicle for TPA. A logarithmic transformation was applied to the data

, List of significantly regulated genes after NM-203 (5 µg/cm 2 ) treatment (unpaired T-test with p<0.05, FC>2). FC: Fold Change

, List of significantly regulated genes after Min-U-Sil 5 Ò, p.20

, µg/cm 2 ) treatment (unpaired T-test with p<0.05, FC>2). FC: Fold Change

, List of significantly regulated genes after TPA (0.05 µg/ml) treatment (unpaired T-test with p<0.05, FC>2). FC: Fold Change

, List of significantly regulated genes after NM-203 (2 µg/cm 2 ) treatment (unpaired T-test with p<0.05, FC>2). FC: Fold Change

, List of significantly regulated genes after NM-203 (5 µg/cm 2 ) treatment (unpaired T-test with p<0.005, FC>4). FC: Fold Change

, List of significantly regulated genes after Min-U-Sil 5 Ò, p.20

, µg/cm 2 ) treatment (unpaired T-test with p<0.005, FC>4). FC: Fold Change

, List of significantly regulated genes after TPA (0.05 µg/ml) treatment (unpaired T-test with p<0.005, FC>4). FC: Fold Change

, List of significantly regulated genes after NM-203 (2 µg/cm 2 ) treatment (unpaired T-test with p<0.005, FC>4). FC: Fold Change

, The top common canonical pathways are highlighted by IPA. Ctrl: H2O; TPA: 12-Otetradecanoylphorbol-13-acetate; DE: Diatomaceous earth; DMSO: Dimethyl sulfoxide; FC: Fold Change