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.

Autor: Brockmeier EK; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK., Basili D; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Park, Sharnbrook, UK., Herbert J; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK., Rendal C; Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Park, Sharnbrook, UK., Boakes L; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Christeyns Food Hygiene, Warrington, UK., Grauslys A; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Computational Biology Facility (CBF), University of Liverpool, Liverpool, UK., Taylor NS; School of Biosciences, University of Birmingham, Birmingham, UK., Danby EB; Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Park, Sharnbrook, UK., Gutsell S; Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Park, Sharnbrook, UK., Kanda R; Institute of Environment, Health and Societies, Brunel University, London, UK., Cronin M; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, UK., Barclay J; Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK., Antczak P; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Computational Biology Facility (CBF), University of Liverpool, Liverpool, UK., Viant MR; School of Biosciences, University of Birmingham, Birmingham, UK., Hodges G; Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Park, Sharnbrook, UK., Falciani F; Department of Biochemistry & System Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Computational Biology Facility (CBF), University of Liverpool, Liverpool, UK. Electronic address: F.Falciani@liverpool.ac.uk.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2022 Nov 25; Vol. 849, pp. 157666. Date of Electronic Publication: 2022 Jul 28.
DOI: 10.1016/j.scitotenv.2022.157666
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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