Evaluation of developmental toxicity using undifferentiated human embryonic stem cells
Identifieur interne : 001989 ( Main/Exploration ); précédent : 001988; suivant : 001990Evaluation of developmental toxicity using undifferentiated human embryonic stem cells
Auteurs : Eui-Man Jung [Corée du Sud] ; Yeo-Ul Choi [Corée du Sud] ; Hong-Seok Kang [Corée du Sud] ; Hyun Yang [Corée du Sud] ; Eui-Ju Hong [Corée du Sud] ; Beum-Soo An [Corée du Sud] ; Jun-Young Yang [Corée du Sud] ; Ki. Hwan Choi [Corée du Sud] ; Eui-Bae Jeung [Corée du Sud]Source :
- Journal of Applied Toxicology [ 0260-437X ] ; 2015-02.
Abstract
An embryonic stem cell test (EST) has been developed to evaluate the embryotoxic potential of chemicals with an in vitro system. In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES) cells. By using surface marker antigens (SSEA‐4, TRA‐1‐60 and TRA‐1‐81), we confirmed undifferentiated conditions of the used hES cells by immunocytochemistry. We assessed the developmental toxicity of embryotoxic chemicals, 5‐fluorouracil, indomethacin and non‐embryotoxic penicillin G in different concentrations for up to 7 days. While expressions of the surface markers were not significantly affected, the embryotoxic chemicals influenced their response to pluripotent ES cell markers, such as OCT‐4, NANOG, endothelin receptor type B (EDNRB), secreted frizzled related protein 2 (SFRP2), teratocarcinoma‐derived growth factor 1 (TDGF1), and phosphatase and tensin homolog (PTEN). Most of the pluripotent ES cell markers were down‐regulated in a dose‐dependent manner after treatment with embryotoxic chemicals. After treatment with 5‐fluorouracil, indomethacin and penicillin G, we observed a remarkable convergence in the degree of up‐regulation of development, cell cycle and apoptosis‐related genes by gene expression profiles using an Affymetrix GeneChips. Taken together, these results suggest that embryotoxic chemicals have cytotoxic effects, and modulate the expression of ES cell markers as well as development‐, cell cycle‐ and apoptosis‐related genes that have pivotal roles in undifferentiated hES cells. Therefore, we suggest that hES cells may be useful for testing the toxic effects of chemicals that could impact the embryonic developmental stage. Copyright © 2014 John Wiley & Sons, Ltd.
An embryonic stem cell test (EST) has been developed to evaluate the potential of chemicals with an in vitro system. In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES) cells. The embryotoxic chemicals influence their response to pluripotent ES cell markers. Our microarray data may be used as indicators for assessment of new chemicals. We define the hES cell viability and embryonic‐specific differentiation by chemicals.
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DOI: 10.1002/jat.3010
Affiliations:
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In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES) cells. By using surface marker antigens (SSEA‐4, TRA‐1‐60 and TRA‐1‐81), we confirmed undifferentiated conditions of the used hES cells by immunocytochemistry. We assessed the developmental toxicity of embryotoxic chemicals, 5‐fluorouracil, indomethacin and non‐embryotoxic penicillin G in different concentrations for up to 7 days. While expressions of the surface markers were not significantly affected, the embryotoxic chemicals influenced their response to pluripotent ES cell markers, such as OCT‐4, NANOG, endothelin receptor type B (EDNRB), secreted frizzled related protein 2 (SFRP2), teratocarcinoma‐derived growth factor 1 (TDGF1), and phosphatase and tensin homolog (PTEN). Most of the pluripotent ES cell markers were down‐regulated in a dose‐dependent manner after treatment with embryotoxic chemicals. After treatment with 5‐fluorouracil, indomethacin and penicillin G, we observed a remarkable convergence in the degree of up‐regulation of development, cell cycle and apoptosis‐related genes by gene expression profiles using an Affymetrix GeneChips. Taken together, these results suggest that embryotoxic chemicals have cytotoxic effects, and modulate the expression of ES cell markers as well as development‐, cell cycle‐ and apoptosis‐related genes that have pivotal roles in undifferentiated hES cells. Therefore, we suggest that hES cells may be useful for testing the toxic effects of chemicals that could impact the embryonic developmental stage. Copyright © 2014 John Wiley & Sons, Ltd.</div><div type="abstract">An embryonic stem cell test (EST) has been developed to evaluate the potential of chemicals with an in vitro system. In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES) cells. The embryotoxic chemicals influence their response to pluripotent ES cell markers. Our microarray data may be used as indicators for assessment of new chemicals. We define the hES cell viability and embryonic‐specific differentiation by chemicals.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li></country></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Jung, Eui An" sort="Jung, Eui An" uniqKey="Jung E" first="Eui-Man" last="Jung">Eui-Man Jung</name></noRegion><name sortKey="An, Beum Oo" sort="An, Beum Oo" uniqKey="An B" first="Beum-Soo" last="An">Beum-Soo An</name><name sortKey="Choi, Ki Hwan" sort="Choi, Ki Hwan" uniqKey="Choi K" first="Ki. Hwan" last="Choi">Ki. Hwan Choi</name><name sortKey="Choi, Yeo L" sort="Choi, Yeo L" uniqKey="Choi Y" first="Yeo-Ul" last="Choi">Yeo-Ul Choi</name><name sortKey="Hong, Eui U" sort="Hong, Eui U" uniqKey="Hong E" first="Eui-Ju" last="Hong">Eui-Ju Hong</name><name sortKey="Jeung, Eui Ae" sort="Jeung, Eui Ae" uniqKey="Jeung E" first="Eui-Bae" last="Jeung">Eui-Bae Jeung</name><name sortKey="Jeung, Eui Ae" sort="Jeung, Eui Ae" uniqKey="Jeung E" first="Eui-Bae" last="Jeung">Eui-Bae Jeung</name><name sortKey="Kang, Hong Eok" sort="Kang, Hong Eok" uniqKey="Kang H" first="Hong-Seok" last="Kang">Hong-Seok Kang</name><name sortKey="Yang, Hyun" sort="Yang, Hyun" uniqKey="Yang H" first="Hyun" last="Yang">Hyun Yang</name><name sortKey="Yang, Jun Oung" sort="Yang, Jun Oung" uniqKey="Yang J" first="Jun-Young" last="Yang">Jun-Young Yang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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