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Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing

Baines, RP; Wolton, K; Thompson, CRL; (2021) Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing. Toxicological Sciences , 183 (2) pp. 302-318. 10.1093/toxsci/kfab097. Green open access

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Abstract

A critical aspect of toxicity evaluation is developmental and reproductive toxicity (DART) testing. Traditionally, DART testing has been conducted in vivo in mammalian model systems. New legislation aimed at reducing animal use and the prohibitive costs associated with DART testing, together with a need to understand the genetic pathways underlying developmental toxicity means there is a growing demand for alternative model systems for toxicity evaluation. Here we explore the potential of the eukaryotic social amoeba Dictyostelium discoideum, which is already widely used as a simple model system for cell and developmental biology, as a potential nonanimal model for DART testing. We developed assays for high-throughput screening of toxicity during D. discoideum growth and development. This allowed the toxicity of a broad range of test compounds to be characterized, which revealed that D. discoideum can broadly predict mammalian toxicity. In addition, we show that this system can be used to perform functional genomic screens to compare the molecular modes of action of different compounds. For example, genome-wide screens for mutations that affect lithium and valproic acid toxicity allowed common and unique biological targets and molecular processes mediating their toxicity to be identified. These studies illustrate that D. discoideum could represent a predictive nonanimal model for DART testing due to its amenability to high-throughput approaches and molecular genetic tractability.

Type: Article
Title: Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/toxsci/kfab097
Publisher version: http://dx.doi.org/10.1093/toxsci/kfab097
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Developmental toxicity, Dictyostelium discoideum, Nonanimal model; social amoeba, Teratogen, genetics, high throughput
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10135798
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