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Peer-reviewedCC BY 4.0NAM journal

Activation of the ecdysone receptor agonism AOP (AOP4) in Drosophila S2 cells: a mechanistic in vitro model

  1. 1Wageningen University and Research, Droevendaalsesteeg 4, Wageningen, PB, 6708, Netherlands
  2. 2Unilever, Colworth House, Colworth Road, Bedford, MK44 1LQ, UK

Abstract

A next generation environmental risk assessment encompasses a more mechanistic approach to understanding toxicity by employing New Approach Methodologies (NAMs). Despite the essential role invertebrates have in maintaining the ecosystem, invertebrate specific traits are often overlooked in development of NAMs. Here we investigate the potential of the Drosophila melanogaster S2 cell line to serve as an insect specific in vitro screening assay coupled to the ecdysone receptor agonism Adverse Outcome Pathway (AOP4). The ability of the S2 cells to portray the initial Key Events (KE) of the AOP4 was tested by studying expression profiles of transcription factors involved in early developmental regulation. The results show a dose and time dependent response to ecdysone exposure which is in line with gene expression profile seen in vivo and described in the AOP4. These findings lay the foundation for further development of the invertebrate specific cell-based assay that can be used for early screening of chemicals and offers a mechanistic method for hazard identification contributing to a more relevant and robust mechanistic based risk assessment.

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BibTeX
@article{đarmati2026activation,
  title = {{Activation of the ecdysone receptor agonism AOP (AOP4) in Drosophila S2 cells: a mechanistic in vitro model}},
  author = {Rebeka Đarmati and David Gómez-Blanco and Samantha Hughes and Paul L Carmichael and Bruno Campos and Nico W Van den Brink},
  journal = {NAM journal},
  year = {2026},
  month = oct,
  doi = {10.1016/j.namjnl.2026.100147},
  url = {https://doi.org/10.1016/j.namjnl.2026.100147},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Activation of the ecdysone receptor agonism AOP (AOP4) in Drosophila S2 cells: a mechanistic in vitro model
AU  - Rebeka Đarmati
AU  - David Gómez-Blanco
AU  - Samantha Hughes
AU  - Paul L Carmichael
AU  - Bruno Campos
AU  - Nico W Van den Brink
PY  - 2026
DA  - 2026/10/13
JO  - NAM journal
DO  - 10.1016/j.namjnl.2026.100147
UR  - https://doi.org/10.1016/j.namjnl.2026.100147
AB  - A next generation environmental risk assessment encompasses a more mechanistic approach to understanding toxicity by employing New Approach Methodologies (NAMs). Despite the essential role invertebrates have in maintaining the ecosystem, invertebrate specific traits are often overlooked in development of NAMs. Here we investigate the potential of the Drosophila melanogaster S2 cell line to serve as an insect specific in vitro screening assay coupled to the ecdysone receptor agonism Adverse Outcome Pathway (AOP4). The ability of the S2 cells to portray the initial Key Events (KE) of the AOP4 was tested by studying expression profiles of transcription factors involved in early developmental regulation. The results show a dose and time dependent response to ecdysone exposure which is in line with gene expression profile seen in vivo and described in the AOP4. These findings lay the foundation for further development of the invertebrate specific cell-based assay that can be used for early screening of chemicals and offers a mechanistic method for hazard identification contributing to a more relevant and robust mechanistic based risk assessment.
SN  - 3050-6204
ER  -