7 results on '"Deferme, L."'
Search Results
2. Cell line-specific oxidative stress in cellular toxicity: A toxicogenomics-based comparison between liver and colon cell models
- Author
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Deferme, L., Deferme, L., Briede, J. J., Claessen, S. M. H., Cavill, R., Kleinjans, J. C. S., Deferme, L., Deferme, L., Briede, J. J., Claessen, S. M. H., Cavill, R., and Kleinjans, J. C. S.
- Abstract
Imbalance between high reactive oxygen species formation and antioxidant capacity in the colon and liver has been linked to increased cancer risk. However, knowledge about possible cell line-specific oxidative stress-mechanisms is limited. To explore this further, gene expression data from a human liver and colon cell line (HepG2/Caco-2), both exposed to menadione and H2O2 at six time points (0.5-1-2-4-8 and 24 h) were compared in association with cell cycle distribution. In total, 3164 unique- and 1827 common genes were identified between HepG2 and Caco-2 cells. Despite the higher number of unique genes, most oxidative stress-related genes such as CAT, OGG1, NRF2, NF-kappa B, GCLC, HMOX1 and GSR were differentially expressed in both cell lines. However, cell-specific regulation of genes such as KEAP1 and GCLM, or of the EMT pathway, which are of pathophysiological importance, indicates that oxidative stress induces different transcriptional effects and outcomes in the two selected cell lines. In addition, expression levels and/or -direction of common genes were often different in HepG2 and Caco-2 cells, and this led to very diverse downstream effects as confirmed by correlating pathways to cell cycle changes. Altogether, this work contributes to obtaining a better molecular understanding of cell line-specific toxicity upon exposure to oxidative stress-inducing compounds.
- Published
- 2015
3. Oxidative stress responses in hepatocarcinogenesis: unravelling the mechanisms using a toxicogenomics approach
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Deferme, L., Deferme, L., Deferme, L., and Deferme, L.
- Published
- 2015
4. The challenge of the application of 'omics technologies in chemicals risk assessment: Background and outlook
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Sauer, U.G., Deferme, L., Gribaldo, L., Hackermüller, Jörg, Tralau, T., van Ravenzwaay, B., Yauk, C., Poole, C., Tong, W., Gant, T.W., Sauer, U.G., Deferme, L., Gribaldo, L., Hackermüller, Jörg, Tralau, T., van Ravenzwaay, B., Yauk, C., Poole, C., Tong, W., and Gant, T.W.
- Abstract
This survey by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) highlights that ‘omics technologies are generally not yet applied to meet standard information requirements during regulatory hazard assessment. While they are used within weight-of-evidence approaches to investigate substances’ modes-of-action, consistent approaches for the generation, processing and interpretation of ‘omics data are not applied. To date, no ‘omics technology has been standardised or validated. Best practices for performing ‘omics studies for regulatory purposes (e.g., microarrays for transcriptome profiling) remain to be established. Therefore, three frameworks for (i) establishing a Good-Laboratory Practice-like context for collecting, storing and curating ‘omics data; (ii) ‘omics data processing; and (iii) quantitative WoE approaches to interpret ‘omics data have been developed, that are presented in this journal issue. Application of the frameworks will enable between-study comparison of results, which will facilitate the regulatory applicability of 'omics data. The frameworks do not constitute prescriptive protocols precluding any other data analysis method, but provide a baseline for analysis that can be applied to all data allowing ready cross-comparison. Data analysis that does not follow the frameworks can be justified and the resulting data can be compared with the Framework-based common analysis output.
- Published
- 2017
5. Framework for the quality assurance of ’omics technologies considering GLP requirements
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Kauffmann, H.-M., Kamp, H., Fuchs, R., Chorley, B.N., Deferme, L., Ebbels, T., Hackermüller, Jörg, Perdichizzi, S., Poole, A., Sauer, U.G., Tollefsen, K.E., Tralau, T., Yauk, C., van Ravenzwaay, B., Kauffmann, H.-M., Kamp, H., Fuchs, R., Chorley, B.N., Deferme, L., Ebbels, T., Hackermüller, Jörg, Perdichizzi, S., Poole, A., Sauer, U.G., Tollefsen, K.E., Tralau, T., Yauk, C., and van Ravenzwaay, B.
- Abstract
‘Omics technologies are gaining importance to support regulatory toxicity studies. Prerequisites for performing ‘omics studies considering GLP principles were discussed at the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Workshop Applying ‘omics technologies in Chemical Risk Assessment. A GLP environment comprises a standard operating procedure system, proper pre-planning and documentation, and inspections of independent quality assurance staff. To prevent uncontrolled data changes, the raw data obtained in the respective ‘omics data recording systems have to be specifically defined. Further requirements include transparent and reproducible data processing steps, and safe data storage and archiving procedures. The software for data recording and processing should be validated, and data changes should be traceable or disabled. GLP-compliant quality assurance of ‘omics technologies appears feasible for many GLP requirements. However, challenges include (i) defining, storing, and archiving the raw data; (ii) transparent descriptions of data processing steps; (iii) software validation; and (iv) ensuring complete reproducibility of final results with respect to raw data. Nevertheless, ‘omics studies can be supported by quality measures (e.g., GLP principles) to ensure quality control, reproducibility and traceability of experiments. This enables regulators to use ‘omics data in a fit-for-purpose context, which enhances their applicability for risk assessment.
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- 2017
6. Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop
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Buesen, R., Chorley, B.N., da Silva Lima, B., Daston, G., Deferme, L., Ebbels, T., Gant, T.W., Goetz, A., Greally, J., Gribaldo, L., Hackermüller, Jörg, Hubesch, B., Jennen, D., Johnson, K., Kanno, J., Kauffmann, H.-M., Laffont, M., McMullen, P., Meehan, R., Pemberton, M., Perdichizzi, S., Piersma, A.H., Sauer, U.G., Schmidt, K., Seitz, H., Sumida, K., Tollefsen, K.E., Tong, W., Tralau, T., van Ravenzwaay, B., Weber, R.J.M., Worth, A., Yauk, C., Poole, A., Buesen, R., Chorley, B.N., da Silva Lima, B., Daston, G., Deferme, L., Ebbels, T., Gant, T.W., Goetz, A., Greally, J., Gribaldo, L., Hackermüller, Jörg, Hubesch, B., Jennen, D., Johnson, K., Kanno, J., Kauffmann, H.-M., Laffont, M., McMullen, P., Meehan, R., Pemberton, M., Perdichizzi, S., Piersma, A.H., Sauer, U.G., Schmidt, K., Seitz, H., Sumida, K., Tollefsen, K.E., Tong, W., Tralau, T., van Ravenzwaay, B., Weber, R.J.M., Worth, A., Yauk, C., and Poole, A.
- Abstract
Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data. The workshop participants confirmed the relevance of these Frameworks to facilitate the regulatory applicability and use of 'omics data, and the workshop discussions provided input for their further elaboration. Additionally, the key objective (iv) to establish approaches to connect 'omics perturbations to phenotypic alterations was addressed. Generally, it was considered promising to strive to link gene expression changes and pathway perturbations to the phenotype by mapping them to specific adverse outcome pathways. While further work is necessary before gene expression changes can be used to establish safe levels of substance exposure, the ECETOC workshop provided important incentives towards achieving this goal.
- Published
- 2017
7. An in vitro air-liquid interface inhalation platform for petroleum substances and constituents.
- Author
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Verstraelen S, Jacobs A, Van Laer J, Hollanders K, Van Deun M, Bertels D, Brabers R, Witters H, Remy S, Geerts L, Deferme L, and Frijns E
- Subjects
- A549 Cells, Cell Line, Cell Survival, Humans, Inhalation Exposure, Pilot Projects, Petroleum
- Abstract
The goal is to optimize and show the validity of an in vitro method for inhalation testing of petroleum substances and their constituents at the air-liquid interface (ALI). The approach is demonstrated in a pilot study with ethylbenzene (EB), a mono-constituent petroleum substance, using a human alveolar epithelial cell line model. This included the development and validation of a generation facility to obtain EB vapors and the optimization of an exposure system for a negative control (clean air, CA), positive control (nitrogen dioxide), and EB vapors. The optimal settings for the VITROCELL® 24/48 system were defined. Cytotoxicity, cell viability, inflammation, and oxidative stress were assessed in A549 after exposure to EB vapors. A concentration-dependent significant decrease in mean cell viability was observed after exposure, which was confirmed by a cytotoxicity test. The oxidative stress marker superoxide dismutase 2 was significantly increased, but no concentration-response was observed. A concentration-dependent significant increase in pro-inflammatory markers C-C motif chemokine ligand 2, interleukin (IL)6, and IL8 was observed for EB-exposed A549 cells compared to CA. The data demonstrated consistency between in vivo air concentrations at which adverse respiratory effects were observed and ALI-concentrations affecting cell viability, provided that the actual measured in vitro delivery efficiency of the compound was considered. It can be concluded that extrapolating in vitro air concentrations (adjusted for delivery efficiency and absorption characteristics and applied for testing cell viability) to simulate in vivo air concentrations may be a promising method to screen for acute inhalation toxicity.
- Published
- 2021
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