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

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概要

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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 omepra-zole-, 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 aspirin-treated rat livers as well as rat hepatocytes, and for glutathione deficiency-related genes were high in ome-prazole-, 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.

• 日本トキシコロジー学会の論文
• 2006-12-15

著者

• NAGAO Taku

  National Institute of Health Sciences

• Nagao Taku

  Food Safety Commission Of Japan

• Nagao Taku

  Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit

• Nagao Taku

  Laboratory Of Pharmacology And Toxicology Graduate School Of Pharmaceutical Sciences The University

• Ono Atsushi

  Toxicogenomics Project National Institute Of Biomedical Innovation:national Institute Of Health Scie

• Kiyosawa Naoki

  Toxicogenomics Project National Inst. Of Biomedical Innovation

• Kiyosawa Naoki

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Miwa Satoko

  Exploratory Toxicology & Dmpk Research Laboratories Tanabe Seiyaku Co. Ltd.

• MIZUKAWA Yumiko

  Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liber

• MIYAGISHIMA Toshikazu

  Toxicogenomics Project, National Institute of Biomedical Innovation

• URUSHIDANI Tetsuro

  Toxicogenomics Project, National Institute of Biomedical Innovation

• Shimizu Toshinobu

  Toxicology Laboratory, Pharmaceuticals Research Unit, Research & Development Division, Mitsubishi Ph

• Suzuki Takamasa

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Urushidani Tetsuro

  Toxicogenomics Project National Institute Of Biomedical Innovation:department Of Pathophysiology Dos

• Urushidani Tetsuro

  Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit

• Miyagishima Toshikazu

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Uehara Takeki

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Shiwaku Kouji

  Toxicogenomics Project National Institute Of Biomedical Innovation

• OMURA Ko

  Toxicogenomics Project, National Institute of Biomedical Innovation

• HIRODE Mitsuhiro

  Toxicogenomics Project, National Institute of Biomedical Innovation

• Omura Ko

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Mizukawa Yumiko

  Toxicogenomics Project National Institute Of Biomedical Innovation:department Of Pathophysiology Fac

• Shimizu Toshinobu

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Nagao Taku

  National Institute Of Health Sci.

• Hirode Mitsuhiro

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Ono Atsushi

  Toxicogenomics Project National Institute Of Biomedical Innovation:national Institute Of Health Scie

• Urushidani Tetsuro

  Toxicogenomics Project National Institute Of Biomedical Innovation

• Ono Atsushi

  Toxicogenomics Informatics Project, National Institute of Biomedical Innovation

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