Mus musculus
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ABSTRACT:
PROVIDER: PRJNA128811 | ENA |
REPOSITORIES: ENA
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Project description:Background: Information on the carcinogenic potential of chemicals is only availably for High Production Volume products. There is however, a pressing need for alternative methods allowing for the chronic toxicity of substances, including carcinogenicity, to be detected earlier and more reliably. Here we applied advanced genomics to a cellular transformation assay to identify gene signatures useful for the prediction of risk for carcinogenicity. Methods: Genome wide gene expression analysis and qRT-PCR were applied to untransformed and transformed Balb/c 3T3 cells that exposed to 2, 4-diaminotoluene (DAT), benzo(a)pyrene (BaP), 2-Acetylaminoflourene (AAF) and 3-methycholanthrene (MCA) for 24h and 120h, at different concentrations, respectively. Furthermore, various bioinformatics tools were used to identify gene signatures predicting for the carcinogenic risk. Results: Bioinformatics analysis revealed distinct datasets for the individual chemicals tested while the number of significantly regulated genes increased with ascending treatment concentration of the cell cultures. Filtering of the data revealed a common gene signature that comprised of 13 genes whose regulation in cancer tissue has already been established. Strikingly, this gene signature was already identified prior to cell transformation therefore confirming the predictive power of this gene signature in identifying carcinogenic risks of chemicals. Comparison of fold changes determined by microarray analysis and qRT-PCR were in good agreement. Conclusion: Our data describes selective and commonly regulated carcinogenic pathways observed in an easy to use in vitro carcinogenicity assay. Here we defined a set of genes which can serve as a simply assay to predict the risk for carcinogenicity by use of an alternative in vitro testing strategy. Balb/c 3T3 cells were seeded at 200 cells in each 60 x 15 mm culture dish with 4 ml M10F, using six culture dishes for every treatment. When cells reached a confluence of 60-65%, the culture medium was removed and replaced with fresh medium containing all tested chemicals at a specific concentration and two time points (24 and 120h). First we treated the cells both 24h and 120h with concentrations reported in the literature (0.5µM BaP, 50µM DAT, 25µM AAF and 2µM MCA). In a second approach IC20 concentrations were investigated for each chemical at both time points. The concentrations determined for IC20 ranged from 1.5 µM BaP to 700 µM DAT for 24h of treatment, and from 0.1 µM BaP or MCA to 10µM AAF for 120h of treatment. Balb/c 3T3 cells treated with 0.75% DMSO alone were kept as controls. Each experiment was run in triplicate.
2010-10-02 | E-GEOD-22180 | biostudies-arrayexpress
Project description:The rodent carcinogenicity test requires extremely long test term and large examination cost. Therefore, now we need to develop a short term and low cost screening method. We already developed a chemical carcinogenicity short term screening method CARCINOscreenM-BM-.. This study was performed to validate this screening method. We conducted 28 days-repeated dose experiments in male F344 rats with 4 carcinogens and 2 non-carcinogens, and the gene expression profiles in liver were measureed by custom oligo microarrays. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array. Compound treatments: 4 carcinogens: Hexachloroethane, 1,2,3-Trichloropropane, 1-Amino-2-methylanthraquinone, 3-(4-Chlorophenyl)-1,1-dimethylurea 2 non-carcinogens: 1,2-Dichlorobenzene and Tetracycline hydrochloride
2013-04-02 | E-GEOD-45650 | biostudies-arrayexpress
Project description:The current test strategy for carcinogenicity consists initially of in vivo and in vitro genotoxicity tests. Non-genotoxic carcinogens do not directly induce DNA damage and, as such, go undetected under this test strategy. In a previous study we setup a comparison approach to categorize chemicals having similar modes of action, according to similarity in gene expression. In the current study we will investigate whether this comparison approach can be improved by omptimizing the concentration selection procedure and by testing a concentration range per chemical.
2016-12-23 | GSE53634 | GEO
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:The final goal of this study is to develop a short term and highly accurate prediction method of carcinogenicity based on gene expression profile of rats administrated by carcinogens. We conducted 3 days-, 14 days- and 28 days-repeated dose experiments in male F344 rats with 47 carcinogens and 26 non-carcinogens, and the gene expression profiles in liver were investigated by custom glass microarrays. Supplementary file "73 Compounds for training" indicates 47 carcinogens and 26 non-carcinogens. Supplementary file "15 Compounds for test" lists the other compounds which are for test. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array.
2010-05-19 | E-GEOD-16394 | biostudies-arrayexpress
Project description:The final goal of this study is to develop a short term and highly accurate prediction method of carcinogenicity based on gene expression profile of rats administrated by carcinogens. We conducted 3 days-, 14 days- and 28 days-repeated dose experiments in male F344 rats with 47 carcinogens and 26 non-carcinogens, and the gene expression profiles in liver were investigated by custom glass microarrays. Supplementary file "73 Compounds for training" indicates 47 carcinogens and 26 non-carcinogens. Supplementary file "15 Compounds for test" lists the other compounds which are for test. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array.
2009-06-22 | E-GEOD-16340 | biostudies-arrayexpress
Project description:The rodent carcinogenicity test requires extremely long test term and large examination cost. Therefore, now we need to develop a short term and low cost screening method. We already developed a chemical carcinogenicity short term screening method CARCINOscreen®. This study was performed to validate this screening method. We conducted 28 days-repeated dose experiments in male F344 rats with 4 carcinogens and 2 non-carcinogens, and the gene expression profiles in liver were measureed by custom oligo microarrays.
2013-04-02 | GSE45650 | GEO
Project description:The final goal of this study is to develop a short term and highly accurate prediction method of carcinogenicity based on gene expression profiles of rats subjected to carcinogen exposure. We conducted 3 day-, 14 day- and 28 day-repeated dose experiments in male F344 rats with 47 carcinogens and 26 non-carcinogens, and the gene expression profiles in liver were investigated by custom glass microarrays. Supplementary file "73 Compounds for training" indicates 47 carcinogens and 26 non-carcinogens. Supplementary file "15 Compounds for test" lists the other compounds which are for test. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array.
2009-06-23 | E-GEOD-16743 | 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:Background: Information on the carcinogenic potential of chemicals is only availably for High Production Volume products. There is however, a pressing need for alternative methods allowing for the chronic toxicity of substances, including carcinogenicity, to be detected earlier and more reliably. Here we applied advanced genomics to a cellular transformation assay to identify gene signatures useful for the prediction of risk for carcinogenicity. Methods: Genome wide gene expression analysis and qRT-PCR were applied to untransformed and transformed Balb/c 3T3 cells that exposed to 2, 4-diaminotoluene (DAT), benzo(a)pyrene (BaP), 2-Acetylaminoflourene (AAF) and 3-methycholanthrene (MCA) for 24h and 120h, at different concentrations, respectively. Furthermore, various bioinformatics tools were used to identify gene signatures predicting for the carcinogenic risk. Results: Bioinformatics analysis revealed distinct datasets for the individual chemicals tested while the number of significantly regulated genes increased with ascending treatment concentration of the cell cultures. Filtering of the data revealed a common gene signature that comprised of 13 genes whose regulation in cancer tissue has already been established. Strikingly, this gene signature was already identified prior to cell transformation therefore confirming the predictive power of this gene signature in identifying carcinogenic risks of chemicals. Comparison of fold changes determined by microarray analysis and qRT-PCR were in good agreement. Conclusion: Our data describes selective and commonly regulated carcinogenic pathways observed in an easy to use in vitro carcinogenicity assay. Here we defined a set of genes which can serve as a simply assay to predict the risk for carcinogenicity by use of an alternative in vitro testing strategy.
2010-10-02 | GSE22180 | GEO