| 己烯雌酚在斑马鱼胚胎中的生物蓄积及毒性机制研究 |
| 摘要点击 1821 全文点击 1112 投稿时间：2008-03-09 修订日期：2008-05-12 |
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| 中文关键词 己烯雌酚 斑马鱼胚胎 毒性 QSAR 基因芯片 |
| 英文关键词 diethylstilbestrol zebrafish embryo toxicity quantitative structure-activity relationship (QSAR) gene chip |
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| 中文摘要 |
| 采用HPLC和斑马鱼胚胎发育方法，测定了己烯雌酚（DES）在标准模式种斑马鱼胚胎体内的蓄积规律及胚胎毒性效应，并利用定量活性-结构分析（QSAR）和基因芯片技术，探讨了DES对斑马鱼胚胎的致毒机制.结果表明，在0.2 mg/L DES中暴露24、 48和72 h后，胚胎体内的DES含量分别为（25.78±4.95）、（54.88±7.10）和（71.93±10.55）μg/g；不同起始染毒时间（0 hpf和8 hpf）条件下，亚致死最敏感指标均为72 h孵化率抑制，EC50分别为（0.14±0.09）和（0.33±0.14） mg/L，说明胚胎在发育囊胚期（发育8 h）前对DES暴露更为敏感.QSAR研究发现，DES相对其它酚类类雌激素对斑马鱼胚胎具有较高的毒性，这与它具有较高的TE值（51.121 7 eV）相关；基因芯片研究发现，5 μg/L DES暴露21 d后能导致斑马鱼成鱼部分基因表达异常.DES对斑马鱼具有一定的胚胎毒性和遗传毒性,而生化反应是致毒的关键步骤. |
| 英文摘要 |
| The bioaccumulation regulation and the toxicity of diethylstilbestrol (DES) were studied on zebrafish (Danio rerio) embryos with the methods of HPLC and early life stage test, and the toxic mechanisms were also discussed with the techniques of quantitative structure-activity relationship (QSAR) and gene chips. After the zebrafish embryos exposed at 0.2 mg·L-1 DES for 24, 48 and 72 h, the body levels of DES in zebrafish embryo were (25.78±4.95), (54.88±7.10) and (71.93±10.55) μg/g, respectively. Even exposure started at different time (0 hpf and 8 hpf), the most sensitive sub lethal endpoints were both 72 h delayed hatch, and the EC50 values for them were (0.14±0.09) and (0.33±0.14) mg/L, so that zebrafish embryo was more sensitive to the exposure of DES before the stage of gastrula (8 h after fertilization). QSAR studies found when compared with other phenol-endocrine disrupts, DES was much more toxic, and this related to its higher TE value (52.1217 eV). Meanwhile, when adult zebrafish exposed at 5 μg/L DES for 21 d, it was found by the gene chips that parts of gene expressions would be changed and the genetic toxicity of DES was approved. DES was concluded to be developmental and genetic toxic to zebrafish, and the biochemical reaction-associated process might be the key parameter in determining the toxicity level. |
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