title: Sensitivity to dioxin decreases as zebrafish mature.
abstract: The embryos of teleost fish are exquisitely sensitive to the toxic effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, several lines of evidence suggest that adults are less sensitive to TCDD. To better understand and characterize this difference between early life stage and adults, we exposed zebrafish (Danio rerio) to graded TCDD concentrations at different ages. The LD(50) for embryos exposed at 1 day post-fertilization (dpf) was more than an order of magnitude lower than it was for juveniles exposed at 30 dpf. The latency between exposure and response also increased with age. Embryo toxicity was characterized by marked cardiovascular collapse and heart malformation, whereas juveniles exposed at 30 dpf had no detectable cardiovascular toxicity. In juveniles, the effects of TCDD exposure included stunted growth, altered pigmentation, and skeletal malformations. Furthermore, the transcriptional profile produced in hearts exposed to TCDD as embryos had very little overlap with the transcriptional changes induced by TCDD at 30 dpf. The early cardiotoxic response was associated with fish exposed prior to metamorphosis from the larval to the adult body plan at approximately 14 dpf. Our results show conclusively that the developmental stage at the time of exposure controls the toxic response to TCDD.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin, Madison,Wisconsin 53705, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Lanham
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
authors.forename: Warren
authors.initials: W
authors.lastname: Heideman
mesh_terms: D000014:Abnormalities, Drug-Induced; D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D007928:Lethal Dose 50; D018994:Myosin Light Chains / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011930:Reaction Time / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D018994:Myosin Light Chains; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D029961:Zebrafish Proteins; C532159:myl7 protein, zebrafish; D049452:Green Fluorescent Proteins