Abstract:

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.