ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor-Mediated Developmental Toxicity of Oxygenated PAHs.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- AOP Report: Aryl Hydrocarbon Receptor Activation Leads to Early-Life Stage Mortality via Sox9 Repression-Induced Craniofacial and Cardiac Malformations.Environmental toxicology and chemistry · 2023Pooled it
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- Article
- Aryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Article
- The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Confirmation of high-throughput screening data and novel mechanistic insights into FXR-xenobiotic interactions by orthogonal assays.Current research in toxicology · 2022Article
- Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain.Frontiers in molecular neuroscience · 2022Article
- Gene co-expression network analysis in zebrafish reveals chemical class specific modules.BMC genomics · 2021Article
- Tryptophan Metabolites at the Crossroad of Immune-Cell Interaction via the Aryl Hydrocarbon Receptor: Implications for Tumor Immunotherapy.International journal of molecular sciences · 2021Review
- GerminatedInternational journal of molecular sciences · 2021Article
- A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard.International journal of molecular sciences · 2019Article
- Immobilization ofNanomaterials (Basel, Switzerland) · 2019Article
- Signaling Events Downstream of AHR Activation That Contribute to Toxic Responses: The Functional Role of an AHR-Dependent Long Noncoding RNA (Environmental health perspectives · 2018Article
- Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish.Toxicology and applied pharmacology · 2018Article
- Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists.Reproductive toxicology (Elmsford, N.Y.) · 2018Article
- Development of a high-throughput in vivo screening platform for particulate matter exposures.Environmental pollution (Barking, Essex : 1987) · 2018Article
- Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons.Archives of toxicology · 2018Article
- Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity.JCI insight · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.