{"entity": "journal", "iuid": "acdcc6da8e9c430e803ad3d8796da326", "timestamp": "2026-07-17T05:46:49.533Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Toxicol.%20Appl.%20Pharmacol..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Toxicol.%20Appl.%20Pharmacol."}}, "title": "Toxicol. Appl. Pharmacol.", "issn": "1096-0333", "issn-l": "0041-008X", "publications_count": 2, "publications": [{"entity": "publication", "iuid": "a23dfb26a54f4d608a58aa4db3a52a21", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a23dfb26a54f4d608a58aa4db3a52a21.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a23dfb26a54f4d608a58aa4db3a52a21"}}, "title": "Combination effects of AHR agonists and Wnt/\u03b2-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions.", "authors": [{"family": "Wincent", "given": "Emma", "initials": "E"}, {"family": "Stegeman", "given": "John J", "initials": "JJ"}, {"family": "J\u00f6nsson", "given": "Maria E", "initials": "ME"}], "type": "journal article", "published": "2015-04-15", "journal": {"title": "Toxicol. Appl. Pharmacol.", "issn": "1096-0333", "volume": "284", "issue": "2", "pages": "163-179", "issn-l": "0041-008X"}, "abstract": "Wnt/\u03b2-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between \u03b2-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the \u03b2-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3',4,4',5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with \u03b2-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of \u03b2-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a \u03b2-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of \u03b2-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of \u03b2-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating \u03b2-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes. ", "doi": "10.1016/j.taap.2015.02.014", "pmid": "25711857", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "S0041-008X(15)00065-4"}, {"db": "pmc", "key": "PMC4747639"}, {"db": "mid", "key": "NIHMS666593"}], "notes": [], "created": "2018-10-31T09:51:47.372Z", "modified": "2018-10-31T09:51:47.383Z"}, {"entity": "publication", "iuid": "75f63960003d4fa5891b0ceb7f08a7fc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/75f63960003d4fa5891b0ceb7f08a7fc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/75f63960003d4fa5891b0ceb7f08a7fc"}}, "title": "New CYP1 genes in the frog Xenopus (Silurana) tropicalis: induction patterns and effects of AHR agonists during development.", "authors": [{"family": "J\u00f6nsson", "given": "Maria E", "initials": "ME"}, {"family": "Berg", "given": "Cecilia", "initials": "C"}, {"family": "Goldstone", "given": "Jared V", "initials": "JV"}, {"family": "Stegeman", "given": "John J", "initials": "JJ"}], "type": "comparative study", "published": "2011-01-15", "journal": {"volume": "250", "issn": "1096-0333", "issue": "2", "pages": "170-183", "title": "Toxicol. Appl. Pharmacol.", "issn-l": "0041-008X"}, "abstract": "The Xenopus tropicalis genome shows a single gene in each of the four cytochrome P450 1 (CYP1) subfamilies that occur in vertebrates, designated as CYP1A, CYP1B1, CYP1C1, and CYP1D1. We cloned the cDNAs of these genes and examined their expression in untreated tadpoles and in tadpoles exposed to waterborne aryl hydrocarbon receptor agonists, 3,3',4,4',5-pentachlorobiphenyl (PCB126), \u03b2-naphthoflavone (\u03b2NF), or indigo. We also examined the effects of PCB126 on expression of genes involved in stress response, cell proliferation, thyroid homeostasis, and prostaglandin synthesis. PCB126 induced CYP1A, CYP1B1, and CYP1C1 but had little effect on CYP1D1 (77-, 1.7-, 4.6- and 1.4-fold induction versus the control, respectively). \u03b2NF induced CYP1A and CYP1C1 (26- and 2.5-fold), while, under conditions used, indigo tended to induce only CYP1A (1.9-fold). The extent of CYP1 induction by PCB126 and \u03b2NF was positively correlated to the number of putative dioxin response elements 0-20 kb upstream of the start codons. No morphological effect was observed in tadpoles exposed to 1 nM-10 \u03bcM PCB126 at two days post-fertilization (dpf) and screened 20 days later. However, in 14-dpf tadpoles a slight up-regulation of the genes for PCNA, transthyretin, HSC70, Cu-Zn SOD, and Cox-2 was observed two days after exposure to 1 \u03bcM PCB126. This study of the full suite of CYP1 genes in an amphibian species reveals gene- and AHR agonist-specific differences in response, as well as a much lower sensitivity to CYP1 induction and short-term toxicity by PCB126 compared with in fish larvae. The single genes in each CYP1 subfamily may make X. tropicalis a useful model for mechanistic studies of CYP1 functions.", "doi": "10.1016/j.taap.2010.10.010", "pmid": "20965207", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "S0041-008X(10)00395-9"}, {"db": "pmc", "key": "PMC3014448"}, {"db": "mid", "key": "NIHMS247860"}], "notes": [], "created": "2017-05-04T15:02:03.475Z", "modified": "2020-01-21T13:56:03.084Z"}], "created": "2017-05-09T09:12:34.573Z", "modified": "2020-11-27T13:14:01.165Z"}