2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits zebrafish caudal fin regeneration.
Adult zebrafish completely regenerate their caudal fins following partial amputation. Fin regrowth can easily be monitored in vivo and regenerating tissues can be used to study this dynamic developmental process. In this study we determined that fin regeneration is significantly affected by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Zebrafish caudal fins were partially amputated, and the fish received intraperitoneal (ip) injection of 2.8, 14, or 70 ng/g weight TCDD or vehicle control. By 7 days postamputation, fish exposed to the highest concentration of TCDD regenerated 15% of their fin compared to 65% regrowth in control fish. To determine if this effect was stage specific, zebrafish were exposed to 70 ng/g TCDD on 1, 2, 3, or 4 days postamputation. Fin regeneration was significantly inhibited at all time points following TCDD exposure. TCDD exposure also induced hyperpigmentation in de novo tissue. Zebrafish were dosed with BrdU, following fin amputation and TCDD exposure, to study changes in cell proliferation. By 4 days postamputation, cell proliferation rates were significantly lower in TCDD-exposed fish. TCDD toxicity is mediated through the aryl hydrocarbon receptor (AHR), and RT-PCR experiments confirmed AHR2, ARNT2b, and TCDD-dependent CYP1A expression in the regenerating tissue. These results demonstrate that zebrafish caudal fin regeneration is a unique model to investigate molecular mechanism(s) of TCDD toxicity.
Zodrow
Jeanmarie M
JM
School of Pharmacy, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Tanguay
Robert L
RL
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005121:Extremities / Q000033:anatomy & histology / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis; D015027:Zebrafish / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000096:biosynthesis
C474372:AHR2 protein, zebrafish; D004268:DNA-Binding Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D029961:Zebrafish Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001189:Aryl Hydrocarbon Hydroxylases