biostudies-literatureRude CINational Institute of Environmental Health SciencesNIEHS NIH HHSNational Institutes of HealthNIH HHS50-68https://www.ebi.ac.uk/biostudies/studies/S-EPMC11514837biostudies-literatureUnknown202(1)Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds frequently detected in the environment with widely varying toxicities. Many PAHs activate the aryl hydrocarbon receptor (AHR), inducing the expression of a battery of genes, including xenobiotic metabolizing enzymes like cytochrome P450s (CYPs); however, not all PAHs act via this mechanism. We screened several parent and substituted PAHs in in vitro AHR activation assays to classify their unique activity. Retene (1-methyl-7-isopropylphenanthrene) displays Ahr2-dependent teratogenicity in zebrafish, but did not activate human AHR or zebrafish Ahr2, suggesting a retene metabolite activates Ahr2 in zebrafish to induce developmental toxicity. To investigate the role of metabolism in retene toxicity, studies were performedToxicological sciences : an official journal of the Society of ToxicologyAryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence.PMC11514837T32 ES007060P42 ES016465P30 ES030287Wilson LBLa Du JSchultz KJRude CIColby SMSmith JNLalli PMTanguay RLWaters KMfalseAryl hydrocarbon receptor-dependent toxicity by retene requires metabolic competence.Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds frequently detected in the environment with widely varying toxicities. Many PAHs activate the aryl hydrocarbon receptor (AHR), inducing the expression of a battery of genes, including xenobiotic metabolizing enzymes like cytochrome P450s (CYPs); however, not all PAHs act via this mechanism. We screened several parent and substituted PAHs in in vitro AHR activation assays to classify their unique activity. Retene (1-methyl-7-isopropylphenanthrene) displays Ahr2-dependent teratogenicity in zebrafish, but did not activate human AHR or zebrafish Ahr2, suggesting a retene metabolite activates Ahr2 in zebrafish to induce developmental toxicity. To investigate the role of metabolism in retene toxicity, studies were performed2024-01-01T00:00:00Z2024 Nov2026-07-07T03:17:43.374Z2026-07-07T03:10:44.042ZS-EPMC115148373910786810.1093/toxsci/kfae098