Effects of DMSO on gene expression in human and rat hepatocytes

被引:56
作者
Sumida, Kayo [1 ]
Igarashi, Yoshinobu [2 ]
Toritsuka, Naoki [3 ]
Matsushita, Tomochika [4 ]
Abe-Tomizawa, Kaori [5 ]
Aoki, Mikio [6 ]
Urushidani, Tetsuro [2 ,7 ]
Yamada, Hiroshi [2 ]
Ohno, Yasuo [8 ]
机构
[1] Sumitomo Chem Co Ltd, Environm Hlth Sci Lab, Konohana Ku, Osaka 5548558, Japan
[2] Natl Inst Biomed Innovat, Toxicogenom Informat Project, Osaka, Japan
[3] Eisai & Co Ltd, Appl Pharmacol & New Technol, Biopharmaceut Assessments Core Funct Unit, Tsukuba, Ibaraki, Japan
[4] Chugai Pharmaceut Co Ltd, Dept Safety Assessment, Shizuoka, Japan
[5] Otsuka Pharmaceut Co Ltd, Tokushima Res Inst, Tokushima 77101, Japan
[6] Dainippon Sumitomo Pharma Co Ltd, Genom Sci Labs, Konohana Ku, Osaka, Japan
[7] Doshisha Womens Coll Liberal Arts, Dept Pathophysiol, Fac Pharmaceut Sci, Kyoto, Japan
[8] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan
关键词
gene expression profile; DMSO; human cryopreserved hepatocytes; rat primary cultured hepatocytes; cytotoxicity; DIMETHYL-SULFOXIDE; INDUCED HEPATOTOXICITY; CELLS; DIFFERENTIATION; GENOME;
D O I
10.1177/0960327111399325
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:1701 / 1709
页数:9
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