دورية أكاديمية
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Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish Embryos.

التفاصيل البيبلوغرافية
العنوان: Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish Embryos.
المؤلفون: Schüttler A; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.; Institute for Environmental Research, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany., Jakobs G; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany., Fix JM; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany., Krauss M; Department Effect-Directed Analysis, UFZ, Leipzig, Germany., Krüger J; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany., Leuthold D; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany., Altenburger R; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.; Institute for Environmental Research, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany., Busch W; Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.
المصدر: Environmental health perspectives [Environ Health Perspect] 2021 Apr; Vol. 129 (4), pp. 47006. Date of Electronic Publication: 2021 Apr 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Institute of Environmental Health Sciences Country of Publication: United States NLM ID: 0330411 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-9924 (Electronic) Linking ISSN: 00916765 NLM ISO Abbreviation: Environ Health Perspect Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Research Triangle Park, N. C. National Institute of Environmental Health Sciences.
مواضيع طبية MeSH: Water Pollutants, Chemical* , Zebrafish*, Animals ; Environmental Exposure ; Humans ; Toxicogenetics ; Transcriptome
مستخلص: Background: Humans and environmental organisms are constantly exposed to complex mixtures of chemicals. Extending our knowledge about the combined effects of chemicals is thus essential for assessing the potential consequences of these exposures. In this context, comprehensive molecular readouts as retrieved by omics techniques are advancing our understanding of the diversity of effects upon chemical exposure. This is especially true for effects induced by chemical concentrations that do not instantaneously lead to mortality, as is commonly the case for environmental exposures. However, omics profiles induced by chemical exposures have rarely been systematically considered in mixture contexts.
Objectives: In this study, we aimed to investigate the predictability of chemical mixture effects on the whole-transcriptome scale.
Methods: We predicted and measured the toxicogenomic effects of a synthetic mixture on zebrafish embryos. The mixture contained the compounds diuron, diclofenac, and naproxen. To predict concentration- and time-resolved whole-transcriptome responses to the mixture exposure, we adopted the mixture concept of concentration addition. Predictions were based on the transcriptome profiles obtained for the individual mixture components in a previous study. Finally, concentration- and time-resolved mixture exposures and subsequent toxicogenomic measurements were performed and the results were compared with the predictions.
Results: This comparison of the predictions with the observations showed that the concept of concentration addition provided reasonable estimates for the effects induced by the mixture exposure on the whole transcriptome. Although nonadditive effects were observed only occasionally, combined, that is, multicomponent-driven, effects were found for mixture components with anticipated similar, as well as dissimilar, modes of action.
Discussion: Overall, this study demonstrates that using a concentration- and time-resolved approach, the occurrence and size of combined effects of chemicals may be predicted at the whole-transcriptome scale. This allows improving effect assessment of mixture exposures on the molecular scale that might not only be of relevance in terms of risk assessment but also for pharmacological applications. https://doi.org/10.1289/EHP7773.
التعليقات: Comment in: Environ Health Perspect. 2021 Oct;129(10):104001. (PMID: 34609158)
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المشرفين على المادة: 0 (Water Pollutants, Chemical)
تواريخ الأحداث: Date Created: 20210407 Date Completed: 20211125 Latest Revision: 20220314
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8041271
DOI: 10.1289/EHP7773
PMID: 33826412
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-9924
DOI:10.1289/EHP7773