Universität zu Köln

Pallocca, Giorgia, Grinberg, Marianna, Henry, Margit, Frickey, Tancred, Hengstler, Jan G., Waldmann, Tanja, Sachinidis, Agapios, Rahnenfuehrer, Joerg and Leist, Marcel ORCID: 0000-0002-3778-8693 (2016). Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch. Toxicol., 90 (1). S. 159 - 181. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-0738

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Abstract

The in vitro test battery of the European research consortium ESNATS ('novel stem cell-based test systems') has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow-up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pallocca, Giorgia UNSPECIFIED UNSPECIFIED UNSPECIFIED Grinberg, Marianna UNSPECIFIED UNSPECIFIED UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Frickey, Tancred UNSPECIFIED UNSPECIFIED UNSPECIFIED Hengstler, Jan G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldmann, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahnenfuehrer, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-292268
DOI:	10.1007/s00204-015-1658-7
Journal or Publication Title:	Arch. Toxicol.
Volume:	90
Number:	1
Page Range:	S. 159 - 181
Date:	2016
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1432-0738
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYBROMINATED DIPHENYL ETHERS; HISTONE DEACETYLASE INHIBITORS; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; IN-VITRO; SAFETY ASSESSMENT; RISK-ASSESSMENT; ENVIRONMENTAL CHEMICALS; RESPONSE EVALUATION; VALPROIC ACID Multiple languages Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29226