Research article summary (published 27 Aug 2009):

Differential cytotoxic effects of mono-(2-ethylhexyl) phthalate on blastomere-derived embryonic stem cells and differentiating neurons.

Full Abstract

Potential applications of embryonic stem (ES) cells are not limited to regenerative medicine but can also include in vitro screening of various toxicants. In this study, we established mouse ES cell lines from isolated blastomeres of two-cell stage embryos and examined their potential use as an in vitro system for the study of developmental toxicity. Two ES cell lines were established from 69 blastomere-derived blastocysts (2.9%). The blastomere-derived ES (bm-ES) cells were treated with mono-(2-ethylhexyl) phthalate (MEHP) in an undifferentiated state or after directed differentiation into early neural cell types. We observed significantly decreased cell viability when undifferentiated bm-ES cells were exposed to a high dose of MEHP (1000 microM). The cytotoxic effects of MEHP were accompanied by increased DNA fragmentation, nuclear condensation, and activation of Caspase-3, which are biochemical and morphological features of apoptosis. Compared to undifferentiated bm-ES cells, considerably lower doses of MEHP (50 and 100 microM) were sufficient to induce cell death in early neurons differentiated from bm-ES cells. At the lower doses, the number of neural cells positive for the active form of Caspase-3 was greater than that for undifferentiated bm-ES cells. Thus, our data indicate that differentiating neurons are more sensitive to MEHP than undifferentiated ES cells, and that undifferentiated ES cells may have more efficient defense systems against cytotoxic stresses. These findings might contribute to the development of a new predictive screening method for assessment of hazards for developmental toxicity.

Author information

Author/s: Lim, Chun Kyu (CK); Kim, Suel-Kee (SK); Ko, Duck Sung (DS); Cho, Jea Won (JW); Jun, Jin Hyun (JH); An, Su-Yeon (SY); Han, Jung Ho (JH); Kim, Jong-Hoon (JH); Yoon, Yong-Dal (YD);

Affiliation: Laboratory of Reproductive Endocrinology, Department of Life Science, College of Natural Sciences, Hanyang University, Seongdong-Gu, Seoul, Republic of Korea. seungzzang(-atsign-)paran.com

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Toxicology (Toxicology), published in Ireland. (Language: eng)

Reference: 2009-Oct; vol 264 (issue 3) : pp 145-54

Dates: Created 2009/09/28; Completed 2009/10/13;

PMID: 19720108, status: MEDLINE (last retrieval date: 10/13/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Apoptosis - drug effects Blastomeres - drug effects; metabolism; pathology Caspase 3 - metabolism Cell Differentiation Cell Line Cell Survival - drug effects DNA Fragmentation Diethylhexyl Phthalate - analogs & derivatives; toxicity

Dose-Response Relationship, Drug Embryonic Stem Cells - drug effects; metabolism; pathology Enzyme Activation Mice Neurons - drug effects; metabolism; pathology Plasticizers - toxicity Risk Assessment Time Factors Toxicity Tests

Associated Chemicals: Plasticizers (0) ; Diethylhexyl Phthalate (117-81-7) ; mono-(2-ethylhexyl)phthalate (4376-20-9) ; Casp3 protein, mouse (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-)

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