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
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
1256Subventions
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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