NDLI: Gene-modified embryonic stem cell test to characterize chemical risks.

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Gene-modified embryonic stem cell test to characterize chemical risks.

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Gene-modified embryonic stem cell test to characterize chemical risks.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Koyama, Masayasu Kitada, Kohei Kizu, Akane Takehara, Toshiyuki Hayashi, Masami Tachibana, Daisuke Morita, Takashi Teramura, Takeshi Yoshida, Kayo Wanibuchi, Hideki Fukushima, Shoji
Description	Country affiliation: Japan Author Affiliation: Kitada K ( Department of Obstetrics and Gynecology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Kizu A ( Department of Molecular Genetics, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Teramura T ( Institute of Advanced Clinical Medicine, Faculty of Medicine, Kindai University, 377-2 Onohigashi, Sayama, Osaka, 589-8511, Japan.); Takehara T ( Institute of Advanced Clinical Medicine, Faculty of Medicine, Kindai University, 377-2 Onohigashi, Sayama, Osaka, 589-8511, Japan.); Hayashi M ( Department of Obstetrics and Gynecology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Tachibana D ( Department of Obstetrics and Gynecology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Wanibuchi H ( Department of Pathology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Fukushima S ( Japan Bioassay Research Center, 2445 Hirasawa, Hadano, Kanagawa, 257-0015, Japan.); Koyama M ( Department of Obstetrics and Gynecology, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.); Yoshida K ( Department of Molecular Genetics, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. k-yoshida@med.osaka-cu.ac.jp.); Morita T ( Department of Molecular Genetics, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.)
Abstract	A high-throughput test of cell growth inhibition was performed using mouse embryonic stem (ES) cells to assess chemical toxicities. We herein demonstrated using a 96-well culture plate approach and the MTT assay that this method was suitable for prioritization of chemicals for their cytotoxic properties. In order to categorize chemicals, we used p53 gene-modified mouse ES cells as well as wild-type ES cells. The p53 gene is a well-known tumor suppressor and controls programmed cell death (apoptosis) and cellular senescence that is triggered by DNA-damaging agents such as alkylating agents and radiation. In the present study, p53-deficient ES cells were found to be more resistant to a tumor initiator, diethylnitrosamine (DEN), than wild-type ES cells, suggesting the inhibition of apoptosis or senescence by a dysfunction in p53. Chromosome aberrations were more frequently detected in p53-deficient ES cells than in wild-type cells, indicating genomic instability due to the deletion of p53. Other tumor initiators, methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (NMU), did not reveal apparent differences in cytotoxicity between wild-type and p53-deficient ES cells. Thus, ES test system using gene-modified ES cells may be used to categorize chemicals by detecting their characteristic effects on apoptosis, genotoxic potentials as well as general cytotoxicity.
ISSN	09441344
Issue Number	22
Volume Number	22
e-ISSN	16147499
Journal	Environmental Science and Pollution Research
Language	English
Publisher	Springer
Publisher Date	2015-11-01
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Apoptosis Drug Effects Genetics Embryonic Stem Cells Toxicity Tests Methods Tumor Suppressor Protein P53 Animals Cells, Cultured Dna Damage Diethylnitrosamine Toxicity Mice Journal Article Research Support, Non-u.s. Gov't Discipline Environmental Science Discipline Environmental Chemistry
Content Type	Text
Resource Type	Article
Subject	Environmental Chemistry Health, Toxicology and Mutagenesis Pollution Medicine

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