基因重组Kringle 5蛋白遗传毒性试验研究  

Genetic Toxicity Study about Recombinant Kringle 5 Protein of Plasminogen

作　　者：陈显久[1] 解军[1] 张悦红[1] 牛勃[1] 

机构地区：[1]山西医科大学生物化学与分子生物学教研室,030001

出　　处：《职业与健康》2011年第3期273-275,共3页Occupation and Health

基　　金：山西省科技攻关项目(20080321078);山西医科大学博士启动基金(03200823)

摘　　要：目的检测基因重组Kringle 5蛋白的遗传毒性,为其临床应用提供医学毒理学依据。方法采用国内外遗传毒性试验指导原则推荐的标准组合中Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验检测基因重组Kringle 5蛋白的致突变作用。结果 Ames试验中,Kringle 5蛋白各组回变菌落数均未超过自发回变菌落数2倍,且无剂量-反应关系,故Ames试验结果为阴性,说明Kringle 5蛋白对鼠伤寒沙门菌组氨酸缺陷型TA97、TA98、TA100和TA102 4个菌株均未呈现遗传毒性。小鼠骨髓嗜多染红细胞微核试验中,Kringle 5蛋白各剂量组雌雄性别微核形成率与阴性对照结果比较,差异无统计学意义(P>0.05),表明该Kringle 5蛋白骨髓微核试验结果为阴性。小鼠精子畸形试验中,各实验组与阴性对照组结果比较,差异无统计学意义(P>0.05),表明该Kringle 5蛋白精子畸形试验结果为阴性。结论基因重组Kringle 5蛋白无遗传毒性。[Objective]To detect the genotoxicity of recombinant Kringle 5,and provide toxicological evidence for clinical application.[Methods]Ames test,mice marrow PCE micronucleus test and mice sperm deformity test recommended by the standard combination of domestic and international guidelines for genetic toxicity tests were adopted to detect mutagenicity of recombinant protein Kringle5.[Results]The Ames test＇s result showed the number of colonies of back mutation in did not exceed 2 times in Kringle 5 dose groups,without dose-response relationship.Therefore,the Ames test is negative which indicated that Kringle 5 were not present genetic toxicity on the histidine-deficient Salmonella typhimurium TA97,TA98,TA100,and TA1024 strains.The mice marrow PCE micronucleus test＇s result showed the difference of micronucleus formation rates was not significant between Kringle 5 dose groups and the negative control group（P〉0.05）,indicating the Kringle 5 was negative in the bone marrow micronucleus test.Mouse sperm abnormality test＇s result showed the difference was not significant between each experimental group and the negative control group（P〉0.05）,indicating that the Kringle 5 was negative in sperm abnormality test.[Conclusion]Recombinant Kringle 5 protein has no genotoxicity.

关 键 词：KRINGLE5 AMES试验 微核试验 精子畸形试验 

分 类 号：R114[医药卫生—卫生毒理学]