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Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening

Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening

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TONG, Zhi-Bin, Helena HOGBERG, David KUO, Srilatha SAKAMURU, Menghang XIA, Lena SMIRNOVA, Thomas HARTUNG, David GERHOLD, 2017. Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening. In: Journal of Applied Toxicology. 37(2), pp. 167-180. ISSN 0260-437X. eISSN 1099-1263. Available under: doi: 10.1002/jat.3334

@article{Tong2017Chara-38743, title={Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening}, year={2017}, doi={10.1002/jat.3334}, number={2}, volume={37}, issn={0260-437X}, journal={Journal of Applied Toxicology}, pages={167--180}, author={Tong, Zhi-Bin and Hogberg, Helena and Kuo, David and Sakamuru, Srilatha and Xia, Menghang and Smirnova, Lena and Hartung, Thomas and Gerhold, David} }

2017-05-04T09:35:04Z Xia, Menghang Hogberg, Helena Hartung, Thomas Tong, Zhi-Bin Tong, Zhi-Bin Gerhold, David Hogberg, Helena Kuo, David Sakamuru, Srilatha eng 2017 Smirnova, Lena Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening Sakamuru, Srilatha Xia, Menghang Gerhold, David 2017-05-04T09:35:04Z Hartung, Thomas Smirnova, Lena More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Kuo, David

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