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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Histone Code* ; Mass Spectrometry* ; Protein Processing, Post-Translational*; Teratogens/*analysis ; Toxicity Tests/*methods; Humans ; Proof of Concept Study
    • Abstract:
      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).
      (© 2022. The Author(s).)
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    • Grant Information:
      3S031319 Fonds Wetenschappelijk Onderzoek; 11B4518N Fonds Wetenschappelijk Onderzoek; 12E9716N Fonds Wetenschappelijk Onderzoek; BOF20DOC220 Bijzonder Onderzoeksfonds UGent; SB-141209 Agentschap Innoveren en Ondernemen
    • Accession Number:
      0 (Teratogens)
    • Publication Date:
      Date Created: 20220125 Date Completed: 20220308 Latest Revision: 20220308
    • Publication Date:
      20250114
    • Accession Number:
      PMC8786925
    • Accession Number:
      10.1038/s41598-022-05268-x
    • Accession Number:
      35075221