Gene expression profiles in liver of F344 rat treated with chemical
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Hiroshi Matsumoto
PROVIDER: E-GEOD-45650 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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.
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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.
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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.
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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.
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Project description:The need for an efficient carcinogenicity test prompted this study, in which we used a microarray-based genomics approach, with a short-term in vivo model, in combination with insights from statistical and mechanistic analyses. We performed additional experiments to support the significance of the microarray results. Carcinogens were evaluated based on differences in the mechanisms involved in the response to genotoxic (GTX) carcinogens and non-genotoxic (NGTX) carcinogens. Microarray data were analyzed for 2 time points after treatment with the following 6 carcinogens. The analysis was performed using t-tests to compare the fold changes, and we selected differentially expressed genes (DEGs) and evaluated the reasons for differential expression in terms of cellular pathways and processes. We mapped the DEG-related pathways to analyze cellular processes, and we were able to uncover significant mechanisms that involve critical cellular components, such as CDKN1A (p21) and BAX. In addition, a comparison of the data from two time points showed that the repeated administration model was more effective than a single administration for carcinogen research. The classification analysis of selected DEGs was performed by setting microarray data of 4 carcinogens as test sets; these test sets were evaluated as classifiers. Microarray results were further supported using the Comet and micronucleus assays. It was found that gene expression profiling using microarrays, followed by pathway analysis, was effective in increasing the understanding of the characteristics of different carcinogens, and the efficiency of these methods was exemplified by the short-term (3 day) nature of the animal experiments. The following 10 hepatocarcinogens were used: 2-acetylaminofluorene (53-96-3), diethylnitrosamine (55-18-5), 4-dimethylamino-3'-methyl azobenzene (55-80-1), clofibrate (637-07-0), 1,4-dioxane (123-91-1), DL-ethionine (67-21-0), 1,3-dichloro-2'-propanol (96-23-1), urethane (51-79-6), sodium nitrite (7632-00-0), and methyleugenol (93-15-2). Forty-one data were obtained for the training compounds in this study. We treated rats with one of three compounds or a control for each GTX and NGTX experimental group and measured 2 time points for each group. All experimental procedures were repeated three times. We excluded 1 file that was found to be a failure. Each ‘.CEL’ file obtained as a raw data file was standardized using the RMA (Robust Multi-array Average) algorithm.
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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.
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Project description:Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment. [mRNA profling] 96 hepatic samples in total, 8 control untreated samples, replicates per treated group n=4-6
2014-04-01 | E-GEOD-43977 | 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 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.
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Project description:In this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels. Male Wistar rats were treated by oral gavage with the eight nongenotoxic hepatocarcinogens Phenobarbital sodium (PB), Piperonylbutoxide (PBO), Dehydroepiandrosterone (DHEA), Acetamide (AA), Methapyrilene HCl (MPy), Methylcarbamate (Mcarb), Diethylstilbestrol (DES) and Ethionine (ETH), the two genotoxic carcinogens C.I Direct Black (CIDB) and dimethylnitrosamine (DMN), the two non-hepatocarcinogens Cefuroxime (CFX) and Nifedipine (Nif), and the three compounds with undefined carcinogenic class Cyproterone acetate (CPA), Thioacetamid (TAA) and Wy-14643 (Wy). Depending on the administered compound, livers were taken after 3, 7, or 14 days for histopathological evaluation. From the five animals per treatment group three animals were selected based on the histopathological findings and subjected to molecular profiling using Affymetrix RG-230A arrays (mRNA expression), Agilent G4473A arrays (miRNA expression) and Zeptosens ZeptoMARK reverse arrays (protein expression).
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