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High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities by Steven Wink; Steven Hiemstra; Bram Herpers; Bob van de Water is a Environmental Science article available to read on EtoBox.

What is High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities about?

Adaptive cellular stress responses are paramount in the healthy control of cell and tissue homeostasis and generally activated during toxicity in a chemical-specific manner. Here, we established a platform containing a panel of distinct adaptive stress response reporter cell lines based on BAC-transgenomics GFP tagging in HepG2 cells. Our current panel of eleven BAC-GFP HepG2 reporters together contains (1) upstream sensors, (2) downstream transcription factors and (3) their respective target genes, representing the oxidative stress response pathway (Keap1/Nrf2/Srxn1), the unfolded protein response in the endoplasmic reticulum (Xbp1/Atf4/BiP/Chop) and the DNA damage response (53bp1/p53/p21). Using automated confocal imaging and quantitative single-cell image analysis, we established that all reporters allowed the time-resolved, sensitive and mode-of-action-specific activation of the individual BAC-GFP reporter cell lines as defined by a panel of pathway-specific training compounds. Implementing the temporal pathway activity information increased the discrimination of training compounds. For a set of >30 hepatotoxicants, the induction of Srxn1, BiP, Chop and p21 BAC-GFP reporters co

Who reads High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities?

Author

Steven Wink; Steven Hiemstra; Bram Herpers; Bob van de Water

Publisher

Springer-Verlag; Springer Verlag; Springer Science and Business Media LLC; Society for Mining, Metallurgy and Exploration Inc. (ISSN 0340-5761)

Published

2016

Language

EN

Field

Environmental Science (Life Sciences)