斑马鱼胚胎试验比较4种抗肿瘤药物的毒性☆

背景：目前斑马鱼胚胎毒性试验在国内已广泛应用于环境、农业和生态学领域,但其在药物毒性筛选的应用仍处于起步阶段。目的：运用斑马鱼胚胎试验比较4种常用抗肿瘤药物注射剂的毒性强弱,评估斑马鱼胚胎试验用于药物毒性筛选的效果。方法：挑选6hpf时发育正常的受精卵进行药物暴露。环磷酰胺、盐酸阿糖胞苷、氟尿嘧啶、硫酸长春新碱4种待测药物分别设置7个实验组,包括：5个药物浓度组,空白对照组（Holt Buffer溶液）,助溶剂对照组（含0.5%二甲基亚砜的Holt Buffer溶液）。于72hpf观察斑马鱼胚胎的发育变化,并统计各实验组斑马鱼胚胎的死亡数、孵化数、畸形数以及各种发育缺陷,并据此求取在72hpf时,斑马鱼胚胎畸形率、死亡率、各药物毒力方程、相关系数和95%置信限及LD50、ED50和LD1/ED99。结果与结论：斑马鱼胚胎试验中,测得4种常见抗肿瘤药物注射剂LD50从大到小依次排序为：环磷酰胺〉盐酸阿糖胞苷〉氟尿嘧啶〉硫酸长春新碱。ED50由大到小依次排序为：环磷酰胺〉盐酸阿糖胞苷〉氟尿嘧啶〉硫酸长春新碱。LD1/ED99由大到小依次排序为：硫酸长春新碱〉氟尿嘧啶〉环磷酰胺〉盐酸阿糖胞苷。结果表明,斑马鱼胚胎试验方法可适用于快速有效测试多种药物的毒性及评价药物安全性,达到高通量筛选药物的目的。

Comparison of toxicity of four anti-cancer drug injections through zebrafish embryos test

BACKGROUND：Zebrafish embryo toxicity test in China has been widely used in the field of environment,agriculture and ecology,but for the toxicity of drugs,it is still in its infancy.OBJECTIVE：To compare the toxicity of four common anti-cancer drug injections through zebrafish embryo test to further evaluate the potential of zebrafish embryo test for drug toxicity screening.METHODS：Normal developed fertilized 6 hours post-fertilization eggs were selected for drug exposure.The cyclophosphamide,cytarabine hydrochloride,fluorouracil and vincristine sulfate were divided randomly into seven groups,including five test groups treated with different drug-concentrations,blank control group（Holt Buffer,Control A） and cosolvent control group（Holt Buffer contained 0.05% dimethyl sulfoxide,Control B）.The development of zebrafish embryos were observed at 72 hours post-fertilization,and the death number,hatching number,malformation and other development defects were all recorded.The malformation rate,mortality rate,regression equation,correlation coefficient and 95% confidence limits,LD50,ED50,and LD1/ED99 were calculated accordingly at 72 hours post-fertilization.RESULTS AND CONCLUSION：The results from zebrafish embryo test showed that LD50 of the four drugs ranged from high to low：cyclophosphamide cytarabine hydrochloride fluorouracil vincristine sulphate.ED50 ranged from high to low：cyclophosphamide cytarabine hydrochloride fluorouracil vincristine sulphate.LD1/ED99 ranged from high to low：vincristine sulphate fluorouracil cyclophosphamide cytarabine hydrochloride.Comparison of toxicity of four anti-cancer drugs in zebrafish embryo test suggests that the zebrafish embryo test is suitable for fast-screening and accessing drug toxicity and safety for several drugs,which can be used for high-throughput drug screen.