Bioactivity screening of environmental chemicals using imaging-based high-throughput phenotypic profiling.
Cell painting
High content imaging
High-throughput profiling
ToxCast
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
21
10
2019
revised:
27
12
2019
accepted:
28
12
2019
pubmed:
4
1
2020
medline:
8
8
2020
entrez:
4
1
2020
Statut:
ppublish
Résumé
The present study adapted an existing high content imaging-based high-throughput phenotypic profiling (HTPP) assay known as "Cell Painting" for bioactivity screening of environmental chemicals. This assay uses a combination of fluorescent probes to label a variety of organelles and measures a large number of phenotypic features at the single cell level in order to detect chemical-induced changes in cell morphology. First, a small set of candidate phenotypic reference chemicals (n = 14) known to produce changes in the cellular morphology of U-2 OS cells were identified and screened at multiple time points in concentration-response format. Many of these chemicals produced distinct cellular phenotypes that were qualitatively similar to those previously described in the literature. A novel workflow for phenotypic feature extraction, concentration-response modeling and determination of in vitro thresholds for chemical bioactivity was developed. Subsequently, a set of 462 chemicals from the ToxCast library were screened in concentration-response mode. Bioactivity thresholds were calculated and converted to administered equivalent doses (AEDs) using reverse dosimetry. AEDs were then compared to effect values from mammalian toxicity studies. In many instances (68%), the HTPP-derived AEDs were either more conservative than or comparable to the in vivo effect values. Overall, we conclude that the HTPP assay can be used as an efficient, cost-effective and reproducible screening method for characterizing the biological activity and potency of environmental chemicals for potential use in in vitro-based safety assessments.
Identifiants
pubmed: 31899216
pii: S0041-008X(19)30484-3
doi: 10.1016/j.taap.2019.114876
pmc: PMC8409064
mid: NIHMS1687283
pii:
doi:
Substances chimiques
Environmental Pollutants
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
114876Subventions
Organisme : Intramural EPA
ID : EPA999999
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None
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