Effects of DMSO on gene expression in human and rat hepatocytes

Human and Experimental Toxicology - Tập 30 Số 10 - Trang 1701-1709 - 2011
Kayo Sumida1, Yoshinobu Igarashi2, Naoki Toritsuka3, Tomochika Matsushita4, Kaori Abe-Tomizawa5, Mikio Aoki6, Tetsuro Urushidani7,2, Hiroshi Yamada2, Yasuo Ohno8
1Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku, Osaka, Japan
2Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan
3Applied Pharmacology & New Technologies, Biopharmaceutical Assessments Core Function Unit, Eisai Co., Ltd., Tsukuba, Ibaraki, Japan
4Safety Assessment Department, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan
5Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd, Kawauchi-cho, Tokushima, Japan
6Genomic Science Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Konohana-ku, Osaka, Japan
7Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan
8National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan

Tóm tắt

Dimethyl sulfoxide (DMSO) is a very common organic solvent used for dissolving lipophilic substances, for example for in vitro cell-based assays. At the same time, DMSO is known to be cytotoxic at high concentrations. Therefore, it is important to define threshold concentrations of DMSO for cells but relevant data at the molecular level are very limited. We have focused on conducting microarray analyses of human and rat hepatocytes treated with more than 100 chemicals in attempts to identify candidate biomarker genes. In the present study, the effects of DMSO on gene expression and cytotoxicity were assessed in human cryopreserved hepatocytes and rat primary cultured hepatocytes. A cytotoxicity test with lactate dehydrogenase (LDH) activity demonstrated DMSO to be noncytotoxic up to a concentration of 2% (v/v) in both cases and there were only few effects on the gene expression profiles up to 0.5% (v/v). The observed differences from controls were considered to be of little toxicological importance, but still need to be taken into account in interpretation of findings when DMSO is used at high concentration.

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Tài liệu tham khảo

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