杂多化合物九钨三钛硅酸盐的毒性研究  

The toxicological effects of polyoxometalates α-Ti_3

作　　者：梅树江[1] 刘娅[2] 王宝贵[2] 张桂英[2] 章培标[3] 赵林伊[2] 

机构地区：[1]深圳市疾病预防控制中心,广东深圳518055 [2]吉林大学公共卫生学院,吉林长春130021 [3]中国科学院长春应用化学研究所,吉林长春130022

出　　处：《癌变．畸变．突变》2010年第6期465-468,共4页Carcinogenesis,Teratogenesis & Mutagenesis

摘　　要：目的：对杂多化合物九钨三钛硅酸盐（α-K8H2[SiW9Ti3O40].15H2O,α-Ti3）的毒性进行研究,为其临床应用提供科学依据。方法：采用小鼠经口急性毒性试验、蓄积毒性试验、Ames试验、中国仓鼠卵巢细胞（CHO）染色体畸变试验和细胞毒性试验对α-Ti3毒性进行检测。结果：小鼠经口急性毒性试验的半数致死剂量（LD50）为2 055.36 mg/kg,属低毒物质;蓄积毒性试验提示α-Ti3在体内蓄积系数K〉5,为轻度蓄积;Ames试验在每皿31.3~500μg浓度范围内,无论加S9与否,每皿菌落回变数均未超过阴性对照组的两倍;中国仓鼠卵巢细胞染色体畸变试验在40~320μg/ml范围内,无论加S9与否,CHO染色体畸变率与阴性对照组比较均无明显增加。对大鼠外周血细胞毒性和骨髓细胞毒性的半数抑制浓度（IC50）分别为0.135、0.223 mg/ml,高于S180腹水瘤细胞和小鼠肝癌细胞,说明该药对正常细胞的毒性作用较低。结论：在本实验条件下,杂多化合物九钨三钛硅酸盐属低毒物质,提示其具有良好的应用前景。OBJECTIVE： To investigate the toxicity of polyoxometalates α-K8H2[SiW9Ti3O40]·15H2O（α-Ti3） for clinic application.METHODS： The studies were conducted with acute toxicity test,cumulative toxicity test,Ames test and chromosome aberration test on CHO cell in vitro and cytotoxicity test.RESULTS： LD50 in mice was 2 055.36 mg/kg,α-Ti3 was a low-grade toxicity compound.The cumulation coefficient was exceed 5,it showed α-Ti3 was low cumulation.The results of Ames test showed no mutagenic effects with the concentration ranged from 31.3 to 500 μg/utensil with or without S9 mixture added.The chromosome aberration ratio of α-Ti3 groups was no significant discrepancy compared with the control on CHO cells,with the concentration ranged from 40 to 320 μg/ml with or without S9 mixture added.IC50 of medulla cells and peripheral blood lymphocytes of rats in vitro treated with α-Ti3 were 0.223 and 0.135 mg/ml,respectively.However,IC50 of S180 ascites tumor cell and mice hepatoma carcinoma cell were low.It showed the toxicity of α-Ti3 was low on normal cell.CONCLUSION： The toxicity of α-Ti3 was low and no mutagenicity was observed in this experiment,the results suggested that α-Ti3 should be a better anti-tumor drug in clinic chemical theropy.

关 键 词：杂多化合物 急性毒性 蓄积毒性 致突变试验 细胞毒性 

分 类 号：R979.1[医药卫生—药品] R994[医药卫生—药学]