Transferability of a modified embryonic stem cell test using a new endpoint for developmental neurotoxicity

Dae Hyun Baek, Su Yeon An, Jae Hyun Park, Youngju Choi, Ki Dae Park, Jin Wook Kang, Kyoung Suk Choi, Sung Hee Park, Min Young Whang, Jiyou Han, Jong-Hoon Kim, Hyung Soo Kim, Dongho Geum, Tae Moo Yoo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We developed and analyzed a new surrogate endpoint of the mouse embryonic stem cell test (EST) for developmental neurotoxicity. To determine the sensitivity, specificity, and transferability of the new endpoint, a pre-validation team from three independent laboratories optimized and standardized the protocol for neuronal differentiation of mouse embryonic stem cells (mESCs) by measuring the neuronal differentiation rates of mESCs under different culture conditions, such as the presence or absence of basic fibroblast growth factor (bFGF) in the growth media and varying lengths of culture. In addition, a component ratio of neuronal cells was measured by using flow cytometry analysis of β-III tubulin (Tuj1)-positive cells and real-time polymerase chain reaction analysis of microtubule-associated protein 2 (MAP2) mRNA. Our results showed that the best growth was achieved by culturing mESCs for 12 d in N2B27 medium without bFGF or ascorbic acid. Lead (II) acetate and aroclor 1254 were used to test the usefulness of the new endpoint. When we used the known ID50 values for lead (II) acetate in the EST model, it was classified as non-embryotoxic; however, when we used the new ID50 values that we determined in this study, it was classified as weakly embryotoxic. Aroclor 1254 and penicillin G were also classified as weakly embryotoxic and non-embryotoxic compounds, respectively, when cardiac and neuronal differentiation ID50 values were used. Therefore, our new surrogate endpoint for developmental neurotoxicity is not only sensitive and specific but also transferable among laboratories.

Original languageEnglish
Pages (from-to)118-130
Number of pages13
JournalToxicology Mechanisms and Methods
Volume22
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1

Keywords

  • Aroclor 1254
  • Developmental neurotoxicity
  • Embryonic stem cell test
  • In vitro toxicity test
  • Lead (II) acetate
  • Mouse embryonic stem cell

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Baek, D. H., An, S. Y., Park, J. H., Choi, Y., Park, K. D., Kang, J. W., Choi, K. S., Park, S. H., Whang, M. Y., Han, J., Kim, J-H., Kim, H. S., Geum, D., & Yoo, T. M. (2012). Transferability of a modified embryonic stem cell test using a new endpoint for developmental neurotoxicity. Toxicology Mechanisms and Methods, 22(2), 118-130. https://doi.org/10.3109/15376516.2011.603394