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Title: Gene expression profiling in rat liver treated with compounds inducing phospholipidosis

Abstract

We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.

Authors:
 [1];  [2];  [2];  [3];  [4];  [2]
  1. Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka, 532-8686 (Japan)
  2. Toxicogenomics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, 567-0085 (Japan)
  3. Food Safety Commission of Japan, Chiyoda-ku, Tokyo, 100-8989 (Japan)
  4. National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501 (Japan)
Publication Date:
OSTI Identifier:
21140863
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 229; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2008.01.036; PII: S0041-008X(08)00047-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIHISTAMINICS; BIOLOGICAL MARKERS; CARBON TETRACHLORIDE; CHLORAMPHENICOL; CHLORPROMAZINE; COUMARIN; DIAGNOSIS; GENES; IMIPRAMINE; LIVER; PHENOTYPE; POLAR-CAP ABSORPTION; RATS; SINGLE INTAKE; TAMOXIFEN; TETRACYCLINES; TIME DEPENDENCE; TOXICITY

Citation Formats

Hirode, Mitsuhiro, Toxicogenomics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, 567-0085, Ono, Atsushi, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Miyagishima, Toshikazu, Nagao, Taku, Ohno, Yasuo, Urushidani, Tetsuro, and Department of Pathophysiology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.01.036.
Hirode, Mitsuhiro, Toxicogenomics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, 567-0085, Ono, Atsushi, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Miyagishima, Toshikazu, Nagao, Taku, Ohno, Yasuo, Urushidani, Tetsuro, & Department of Pathophysiology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis. United States. https://doi.org/10.1016/j.taap.2008.01.036
Hirode, Mitsuhiro, Toxicogenomics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, 567-0085, Ono, Atsushi, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Miyagishima, Toshikazu, Nagao, Taku, Ohno, Yasuo, Urushidani, Tetsuro, and Department of Pathophysiology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395. 2008. "Gene expression profiling in rat liver treated with compounds inducing phospholipidosis". United States. https://doi.org/10.1016/j.taap.2008.01.036.
@article{osti_21140863,
title = {Gene expression profiling in rat liver treated with compounds inducing phospholipidosis},
author = {Hirode, Mitsuhiro and Toxicogenomics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, 567-0085 and Ono, Atsushi and National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501 and Miyagishima, Toshikazu and Nagao, Taku and Ohno, Yasuo and Urushidani, Tetsuro and Department of Pathophysiology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395},
abstractNote = {We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.},
doi = {10.1016/j.taap.2008.01.036},
url = {https://www.osti.gov/biblio/21140863}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 229,
place = {United States},
year = {Sun Jun 15 00:00:00 EDT 2008},
month = {Sun Jun 15 00:00:00 EDT 2008}
}