右旋雷贝拉唑钠对CHL细胞染色体畸变的影响实验研究

摘要

目的：通过右旋雷贝拉唑钠对中国仓鼠肺成纤细胞（CHL）染色体畸变试验的研究，预测其是否具有遗传毒性。方法：采用MTT法检测右旋雷贝拉唑钠对CHL的细胞毒性作用，计算药物作用24 h和48 h的半数细胞生长抑制浓度，确定右旋雷贝拉唑钠染色体畸变试验的作用剂量。非代谢活化组和代谢活化组分别加入新鲜配制含右旋雷贝拉唑钠的细胞培养液（包括低、中、高剂量组）5 mL、4.5 mL，代谢活化组再加0.5 mL S9混合液，使24 h组右旋雷贝拉唑钠低、中、高剂量组药物终浓度分别为2、10、50μg·mL-1，48 h组低、中、高剂量组药物终浓度分别为1、5、25μg·mL-1。同时，试验设溶媒对照组和阳性对照组，甲醇-冰醋酸液固定、离心，取沉淀物混匀常规制片，姬姆萨染色。油镜下观察染色体结构畸变种类、频率。每例样本镜检200个中期相细胞，记录染色体数目及形态的变化。结果：右旋雷贝拉唑钠对CHL细胞毒性试验结果显示，24 h时IC50为48.49μg·mL-1，48 h时IC50为21.09μg·mL-1。右旋雷贝拉唑钠对CHL细胞染色体畸变作用的研究结果显示，右旋雷贝拉唑钠低、中、高剂量组分别作用细胞24 h和48 h，在加入S9混合液和未加S9混合液条件下所诱发的染色体畸变数均低于或等于5%，其畸变率与溶媒对照组相比均无显著性差异（P＞0.05）。结论：在本试验条件下，右旋雷贝拉唑钠染色体畸变试验结果为阴性。%Objective:To evaluate the effects of dextral rabeprazole sodium ray Bella on chromosome aberration of China hamster lung ifbroblast cells (CHL), so as to predict whether it has genetic toxicity.Methods: The cytotoxicity dextral rabeprazole sodium on CHL cells was determined by MTT method, and half cell grouth inhibitory concerntration after 24-hour and 48-hour drug action was calculated. The effective dosage of dextral rabeprazole sodium on chromosome aberration was then determined. Freshly prepared dextral rabeprazole sodium cell culture medium (including low, middle, high dose group) was added to non-metabolic activation group (5 mL) as well as metabolic activation group (4.5 mL), and 0.5 mL S9 solution was then added to the metabolic activation group. For the 24 h groups, the concentration of H-ray Bella of cefmetazole sodium in low, medium, and high subgroups were 2, 10, 50 μg·mL-1. For the 48 h groups, the concentration of H - ray Bella of cefmetazole sodium in low, medium, and high subgroups were 1, 5, 25 μg·mL-1. At the same time, the vehicle control group and positive control group were also included for the study. The cells of different groups were ifxed in methanol-glacial acetic acid liquid, and Giemsa staining was performed. The chromosome structure aberration types and frequency were observed under oil microscope. 200 metaphase cells of each sample were selected under microscopy, and changes in chromosome number and morphological were recorded.Results:Our results showed that the IC50 of 24 h was 48.49 μg·mL-1, and 21.09 μg·mL-1 for 48 h. The cell chromosome aberration was less than or egualled to 5% of all the groups. No significant difference was observed among test groups and the control group (P>0.05).Conclusion:The chromosome aberration effects of Rabeprazole Sodium Dextral were negative under the condition of this experiment.