Zodrow Jeanmarie M, Tanguay Robert L
School of Pharmacy, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Toxicol Sci. 2003 Nov;76(1):151-61. doi: 10.1093/toxsci/kfg205. Epub 2003 Aug 12.
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.
成年斑马鱼在尾部被部分截断后能够完全再生其尾鳍。鳍的再生情况可以在体内轻松监测，并且再生组织可用于研究这一动态发育过程。在本研究中，我们确定尾鳍再生受到2,3,7,8 - 四氯二苯并 - p - 二噁英（TCDD）暴露的显著影响。将斑马鱼尾鳍部分截断，然后给鱼腹腔内注射2.8、14或70 ng/g体重的TCDD或溶剂对照。截断后7天，暴露于最高浓度TCDD的鱼鳍再生了其鳍的15%，而对照鱼的鳍再生了65%。为了确定这种影响是否具有阶段特异性，在截断后第1、2、3或4天给斑马鱼暴露于70 ng/g的TCDD。TCDD暴露后在所有时间点鳍的再生均受到显著抑制。TCDD暴露还在新生组织中诱导了色素沉着过度。在鳍截断和TCDD暴露后给斑马鱼注射BrdU，以研究细胞增殖的变化。截断后4天，TCDD暴露的鱼的细胞增殖率显著降低。TCDD毒性是通过芳烃受体（AHR）介导的，RT - PCR实验证实了再生组织中AHR2、ARNT2b和TCDD依赖性CYP1A的表达。这些结果表明斑马鱼尾鳍再生是研究TCDD毒性分子机制的独特模型。
