A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 01 2022
Historique:
received: 05 10 2021
accepted: 07 01 2022
entrez: 25 1 2022
pubmed: 26 1 2022
medline: 9 3 2022
Statut: epublish

Résumé

Toxicoepigenetics is an emerging field that studies the toxicological impact of compounds on protein expression through heritable, non-genetic mechanisms, such as histone post-translational modifications (hPTMs). Due to substantial progress in the large-scale study of hPTMs, integration into the field of toxicology is promising and offers the opportunity to gain novel insights into toxicological phenomena. Moreover, there is a growing demand for high-throughput human-based in vitro assays for toxicity testing, especially for developmental toxicity. Consequently, we developed a mass spectrometry-based proof-of-concept to assess a histone code screening assay capable of simultaneously detecting multiple hPTM-changes in human embryonic stem cells. We first validated the untargeted workflow with valproic acid (VPA), a histone deacetylase inhibitor. These results demonstrate the capability of mapping the hPTM-dynamics, with a general increase in acetylations as an internal control. To illustrate the scalability, a dose-response study was performed on a proof-of-concept library of ten compounds (1) with a known effect on the hPTMs (BIX-01294, 3-Deazaneplanocin A, Trichostatin A, and VPA), (2) classified as highly embryotoxic by the European Centre for the Validation of Alternative Methods (ECVAM) (Methotrexate, and All-trans retinoic acid), (3) classified as non-embryotoxic by ECVAM (Penicillin G), and (4) compounds of abuse with a presumed developmental toxicity (ethanol, caffeine, and nicotine).

Identifiants

pubmed: 35075221
doi: 10.1038/s41598-022-05268-x
pii: 10.1038/s41598-022-05268-x
pmc: PMC8786925
doi:

Substances chimiques

Teratogens 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1256

Subventions

Organisme : Fonds Wetenschappelijk Onderzoek
ID : 3S031319
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 11B4518N
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 12E9716N
Organisme : Bijzonder Onderzoeksfonds UGent
ID : BOF20DOC220
Organisme : Agentschap Innoveren en Ondernemen
ID : SB-141209

Informations de copyright

© 2022. The Author(s).

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Auteurs

Sigrid Verhelst (S)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Bart Van Puyvelde (B)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Sander Willems (S)

Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.

Simon Daled (S)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Senne Cornelis (S)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Laura Corveleyn (L)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Ewoud Willems (E)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Dieter Deforce (D)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Laura De Clerck (L)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Maarten Dhaenens (M)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium. maarten.dhaenens@ugent.be.

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