Mus musculus
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ABSTRACT:
PROVIDER: PRJNA205242 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profiling to recognize specific features of non-genotoxic carcinogens
| PRJNA188549 | ENA
Project description:The current test strategy for carcinogenicity is generally based on in vitro and in vivo genotoxicity assays. Non-genotoxic carcinogens (NGTXC) are negative for genotoxicity and go undetected. Therefore, alternative tests to detect these chemicals are urgently needed. NGTXC act through different modes of action, which complicates the development of such assays. We have demonstrated recently in primary mouse hepatocytes that some, but certainly not all, NGTXC can be categorized according to their mode of action based on feature detection at a gene expression level (Schaap et al. 2012 (PMID 22710402)). Identification of a wider range of chemicals probably requires multiple in vitro systems. In the current study, we describe the added value of using mouse embryonic stem cells. In this study, the focus is on NGTXC, but we also included genotoxic carcinogens and non-carcinogens. This approach enables us to assess the robustness of this method and to evaluate the system for recognizing features of chemicals in general, which is important for application in future risk assessment. Primary mouse hepatocytes and mouse embryonic stem cells were exposed to 26 chemicals (non-genotoxic carcinogens and non-carcinogens) representing diverse modes of action. Upon profiling, an unsupervised comparison approach was applied to recognize similar features at the transcriptomic level. This Series consists of the gene expression data of the primary mouse hepatocytes. The expression data of the mouse embryonic stem cells is submitted separately under another accession number. In this study we tested 26 chemicals of which 16 non-genotoxic carcinogens, 4 genotoxic carcinogens, 2 genotoxic non-carcinogens and 4 non-carcinogens. Specification of the chemicals can be found in the readme file.
2014-10-23 | E-GEOD-44088 | biostudies-arrayexpress
Project description:Under REACH, the European Community Regulation on chemicals, the testing strategy for carcinogenicity is generally based on in vitro and in vivo genotoxicity assays. Given that non-genotoxic carcinogens are negative for genotoxicity, this class of carcinogens will not be detected. Therefore, alternative test are urgently needed. Non-genotoxic carcinogens, however, act through different modes of action, which complicates the development of such an assay. The aim of this study was to investigate whether gene expression profiling in primary mouse hepatocytes can be used to distinguish different modes of action of non-genotoxic carcinogens. Primary mouse hepatocytes were exposed to 16 non-genotoxic carcinogens with diverse modes of action. Upon profiling, pathway analysis was performed to obtain insight into the biological relevance of the observed changes in gene expression. To recognize similarities in mode of action at the transcriptomic level, both a supervised and an unsupervised comparison approach was applied.
2012-06-25 | E-GEOD-35058 | biostudies-arrayexpress
Project description:Expression data from CD-1 mouse liver samples obtained from in-vivo treatment with genotoxic carcinogens, non-genotoxic carcinogens or non-hepatocarcinogens.
| PRJNA191782 | ENA
Project description:Under REACH, the European Community Regulation on chemicals, the testing strategy for carcinogenicity is generally based on in vitro and in vivo genotoxicity assays. Given that non-genotoxic carcinogens are negative for genotoxicity, this class of carcinogens will not be detected. Therefore, alternative test are urgently needed. Non-genotoxic carcinogens, however, act through different modes of action, which complicates the development of such an assay. The aim of this study was to investigate whether gene expression profiling in primary mouse hepatocytes can be used to distinguish different modes of action of non-genotoxic carcinogens.
2012-06-26 | GSE35058 | GEO
Project description:Discriminant for genotoxic and non-genotoxic carcinogens by differentially expressed gene profiling
| PRJNA146129 | ENA
Project description:Dissecting modes of action of non-genotoxic carcinogens in primary mouse hepatocytes.
| PRJNA150837 | ENA
Project description:For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effects markers provide limited mechanistic insight, and are unable to detect exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure. Whole genome gene expression changes were investigated in human blood cells following ex vivo exposure to a range of genotoxic and non-genotoxic carcinogenic compounds using whole genome microarrays. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic genes sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomakers of genotoxic exposure, and possibly even more importantly biomarkers of exposure to non-genotoxic carcinogens since presently no biomarkers are available. Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure
2010-10-22 | GSE24891 | GEO
Project description:To further our investigations for early biomarkers of non-genotoxic carcinogenesis, groups of mice were treated with a range of known or suspected non-genotoxic carcinogens for a period of 28 or 56d and liver tissue harvested for expression profiling. Control groups were treated with appropriate vehicles.
2016-08-26 | GSE68364 | GEO
Project description:The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. Since the results of these 2-year bioassays are not known until quite late during development of new chemical entities, and since the short-term test battery to test for genotoxicity, a characteristic of genotoxic carcinogens, is hampered by low specificity, the identification of early biomarkers for carcinogenicity would be a big step forward. Using gene expression profiles from the livers of rats treated up to 14 days with genotoxic and non-genotoxic carcinogens we previously identified characteristic gene expression profiles for these two groups of carcinogens. We have now added expression profiles from further hepatocarcinogens and from non-carcinogens the latter serving as control profiles. We used these profiles to extract biomarkers discriminating genotoxic from non-genotoxic carcinogens and to calculate classifiers based on the support vector machine (SVM) algorithm. These classifiers then predicted a set of independent validation compound profiles with up to 88% accuracy, depending on the marker gene set. We would like to present this study as proof of the concept that a classification of carcinogens based on short-term studies may be feasible.
2016-04-27 | GSE68110 | GEO