C. elegans toxicant responses vary among genetically diverse individuals.

Autor: Widmayer SJ; Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: sam.widmayer@northwestern.edu., Crombie TA; Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: tcrombie@northwestern.edu., Nyaanga JN; Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: JoyNyaanga2024@u.northwestern.edu., Evans KS; Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: kathrynevans2015@u.northwestern.edu., Andersen EC; Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: erik.andersen@northwestern.edu.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2022 Sep; Vol. 479, pp. 153292. Date of Electronic Publication: 2022 Aug 20.
DOI: 10.1016/j.tox.2022.153292
Abstrakt: The genetic variability of toxicant responses among indisviduals in humans and mammalian models requires practically untenable sample sizes to create comprehensive chemical hazard risk evaluations. To address this need, tractable model systems enable reproducible and efficient experimental workflows to collect high-replication measurements of exposure cohorts. Caenorhabditis elegans is a premier toxicology model that has revolutionized our understanding of cellular responses to environmental pollutants and boasts robust genomic resources and high levels of genetic variation across the species. In this study, we performed dose-response analysis across 23 environmental toxicants using eight C. elegans strains representative of species-wide genetic diversity. We observed substantial variation in EC10 estimates and slope parameter estimates of dose-response curves of different strains, demonstrating that genetic background is a significant driver of differential toxicant susceptibility. We also showed that, across all toxicants, at least one C. elegans strain exhibited a significantly different EC10 or slope estimate compared to the reference strain, N2 (PD1074), indicating that population-wide differences among strains are necessary to understand responses to toxicants. Moreover, we quantified the heritability of responses (phenotypic variance attributable to genetic differences between individuals) to each toxicant exposure and observed a correlation between the exposure closest to the species-agnostic EC10 estimate and the exposure that exhibited the most heritable response. At least 20% of the variance in susceptibility to at least one exposure level of each compound was explained by genetic differences among the eight C. elegans strains. Taken together, these results provide robust evidence that heritable genetic variation explains differential susceptibility across an array of environmental pollutants and that genetically diverse C. elegans strains should be deployed to aid high-throughput toxicological screening efforts.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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