Data-driven learning of narcosis mode of action identifies a CNS transcriptional signature shared between whole organism Caenorhabditis elegans and a fish gill cell line

Erica K. Brockmeier, Danilo Basili, John Herbert, Cecilie Rendal, Leigh Boakes, Arturas Grauslys, Nadine S. Taylor, Emma Butler Danby, Steve Gutsell, Rakesh Kanda, Mark Cronin, Jeff Barclay, Philipp Antczak, Mark R. Viant, Geoff Hodges, Francesco Falciani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

With the large numbers of man-made chemicals produced and released in the environment, there is a need to provide assessments on their potential effects on environmental safety and human health. Current regulatory frameworks rely on a mix of both hazard and risk-based approaches to make safety decisions, but the large number of chemicals in commerce combined with an increased need to conduct assessments in the absence of animal testing makes this increasingly challenging. This challenge is catalysing the use of more mechanistic knowledge in safety assessment from both in silico and in vitro approaches in the hope that this will increase confidence in being able to identify modes of action (MoA) for the chemicals in question. Here we approach this challenge by testing whether a functional genomics approach in C. elegans and in a fish cell line can identify molecular mechanisms underlying the effects of narcotics, and the effects of more specific acting toxicants. We show that narcosis affects the expression of neuronal genes associated with CNS function in C. elegans and in a fish cell line. Overall, we believe that our study provides an important step in developing mechanistically relevant biomarkers which can be used to screen for hazards, and which prevent the need for repeated animal or cross-species comparisons for each new chemical.

Original languageEnglish
Article number157666
Number of pages14
JournalScience of the Total Environment
Volume849
Early online date28 Jul 2022
DOIs
Publication statusPublished - 25 Nov 2022

Bibliographical note

Funding Information:
This work was supported by Unilever Ltd.

Publisher Copyright:
© 2022 The Authors

Keywords

  • Bioinformatics
  • Biomarkers
  • Cross-species analysis
  • Mode of action
  • Narcosis
  • Omics

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

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