Effects of DMSO on gene expression in human and rat hepatocytes

Author:

Sumida Kayo1,Igarashi Yoshinobu2,Toritsuka Naoki3,Matsushita Tomochika4,Abe-Tomizawa Kaori5,Aoki Mikio6,Urushidani Tetsuro27,Yamada Hiroshi2,Ohno Yasuo8

Affiliation:

1. Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku, Osaka, Japan

2. Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan

3. Applied Pharmacology & New Technologies, Biopharmaceutical Assessments Core Function Unit, Eisai Co., Ltd., Tsukuba, Ibaraki, Japan

4. Safety Assessment Department, Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

5. Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Kawauchi-cho, Tokushima, Japan

6. Genomic Science Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Konohana-ku, Osaka, Japan

7. Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe, Kyoto, Japan

8. National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan

Abstract

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.

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Toxicology,General Medicine

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