Effect of the difference in vehicles on gene expression in the rat liver—analysis of the control data in the Toxicogenomics Project Database

Takashima, Kayoko; Mizukawa, Yumiko; Morishita, Katsumi; Okuyama, Manabu; Kasahara, Toshihiko; Toritsuka, Naoki; Miyagishima, Toshikazu; Nagao, Taku; Urushidani, Tetsuro

doi:10.1016/j.lfs.2005.11.010

Cited by 29 publications

(22 citation statements)

References 16 publications

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“…The detailed study information is the same as in the literature (Takashima et al, 2006). Rats were sacrificed at 24 hr after a single dosing of chemicals.…”

Section: Animal Treatmentmentioning

confidence: 99%

“…The detailed information is described in the previous literature (Takashima et al, 2006). Briefly, 3 liver samples out of 5 samples collected in the animal were used for analysis.…”

Section: Microarray Analysismentioning

confidence: 99%

“…Toxicogenomics research requires a high-quality microarray database that covers a sufficient number of well-studied compounds, and such databases are being developed for both public and commercial use (Boverhof and Zacharewski, 2006). The Toxicogenomics Project in Japan (TGP) has been conducted by the collaborative research of 15 pharmaceutical companies, the National Institute of Health Science and the National Institute of Biomedical Innovation, and is a five-year project started from 2002 (Takashima et al, 2006;Urushidani and Nagao, 2005). The TGP database is a toxicogenomics-oriented data-base that consists of microarray data of rat liver, rat hepatocytes and human hepatocytes, as well as traditional toxicological data for 150 compounds.…”

Section: Introductionmentioning

confidence: 99%

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Utilization of a One-Dimensional Score for Surveying Chemical-Induced Changes in Expression Levels of Multiple Biomarker Gene Sets Using a Large-Scale Toxicogenomics Database

et al. 2006

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-A large-scale toxicogenomcis database has now been constructed in the Toxicogenomics Project in Japan (TGP). To facilitate the analytical procedures for such large-scale microarray data, we developed a simple one-dimensional score, named TGP1 which expresses the trend of the changes in expression of biomarker genes as a whole. To evaluate the usefulness of the TGP1 score, microarray data of rat liver and rat hepatocytes deposited in the TGP database were scored for three biomarker gene sets, i.e., carcinogenesis-related, PPARα-regulated and glutathione depletion-related gene sets. The TGP1 scoring system gave reasonable results, i.e., the scores for carcinogenesis-related genes were high in omeprazole-, chlorpromazine-, hexachlorobenzene-, sulfasalazine-and Wy-14,643-treated rat livers, that for PPARα-regulated genes were high in clofibrate-, Wy-14,643-, gemfibrozil-, benzbromarone-and aspirintreated rat livers as well as rat hepatocytes, and for glutathione deficiency-related genes were high in omeprazole-, bromobenzene-, acetaminophen-and coumarin-treated rat liver. We concluded that the TGP1 score is useful for surveying the expression changes in multiple biomarker gene sets for a large-scale toxicogenomics database, which would reduce the time of doing conventional multivariate statistical analysis. In addition, the TGP1 score can be applied to screening of compatible biomarker gene sets between rat liver and rat hepatocytes, like PPARα-regulated gene sets, which will allow us to develop an appropriate in vitro system for drug safety assessment in vivo.

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“…The detailed study information is the same as in the literature (Takashima et al, 2006). Rats were sacrificed at 24 hr after a single dosing of chemicals.…”

Section: Animal Treatmentmentioning

confidence: 99%

“…The detailed information is described in the previous literature (Takashima et al, 2006). Briefly, 3 liver samples out of 5 samples collected in the animal were used for analysis.…”

Section: Microarray Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Utilization of a One-Dimensional Score for Surveying Chemical-Induced Changes in Expression Levels of Multiple Biomarker Gene Sets Using a Large-Scale Toxicogenomics Database

et al. 2006

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“…According to the standard protocol in our project (Takashima et al, 2006), five rats per group were orally administered at three doses with these compounds suspended or dissolved either in 0.5% methylcellulose (MC) solution or corn oil according to their dispersibility. Traditionally, carcinogenicity studies for chemical agents have relied upon the maximally tolerated dose (MTD) as the standard method for high dose selection.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats

et al. 2008

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“…One of the key technologies used in toxicogenomic and pharmacogenomic studies is the microarray, which permits the simultaneous analysis of the expression of a large number of genes. The National Institute of Health Sciences, and the National Institute of Biomedical Innovation, and Japanese pharmaceutical companies began a 5-year collaborative study in the Toxicogenomics Project (TGP1) in Japan from 2002 Takashima et al, 2006). The aim of TGP1 was to construct a large-scale database for use in predicting the toxicity of new molecular entities during the early stages of drug development.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of DNA microarray results in the Toxicogenomics Project (TGP) consortium in Japan

Nakatsu

Igarashi

Ono³

et al. 2012

J. Toxicol. Sci.

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-An important technology used in toxicogenomic drug discovery research is the microarray, which enables researchers to simultaneously analyze the expression of a large number of genes. To build a database and data analysis system for use in assessing the safety of drugs and drug candidates, in 2002 we conducted a 5-year collaborative study in the Toxicogenomics Project (TGP1) in Japan. Experimental data generated by such studies must be validated by different laboratories for robust and accurate analysis. For this purpose, we conducted intra-and inter-laboratory validation studies with participating companies in the second collaborative study in the Toxicogenomics Project (TGP2). Gene expression in the liver of rats treated with acetaminophen (APAP) was independently examined by the participating companies using Affymetrix GeneChip microarrays. The intra-and inter-laboratory reproducibility of the data was evaluated using hierarchical clustering analysis. The toxicogenomics results were highly reproducible, indicating that the gene expression data generated in our TGP1 project is reliable and compatible with the data generated by the participating laboratories.

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Effect of the difference in vehicles on gene expression in the rat liver—analysis of the control data in the Toxicogenomics Project Database

Cited by 29 publications

References 16 publications

Utilization of a One-Dimensional Score for Surveying Chemical-Induced Changes in Expression Levels of Multiple Biomarker Gene Sets Using a Large-Scale Toxicogenomics Database

Utilization of a One-Dimensional Score for Surveying Chemical-Induced Changes in Expression Levels of Multiple Biomarker Gene Sets Using a Large-Scale Toxicogenomics Database

A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats

Evaluation of DNA microarray results in the Toxicogenomics Project (TGP) consortium in Japan

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