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目的检测聚乙二醇修饰降纤酶的遗传毒性。方法应用鼠伤寒沙门菌回复突变试验(Ames试验)、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验检测聚乙二醇修饰降纤酶的遗传毒性。结果 Ames试验结果显示每平皿100、20、4、0.8、0.16 U各个剂量组,在加或不加S9代谢活化系统时对组氨酸缺陷型鼠伤寒沙门菌TA97、TA98、TA100、TA102及TA1535所诱发的回复突变菌落数均与溶剂对照的突变菌落数相近。体外培养CHO细胞染色体畸变试验结果显示2.5、5.0和10.0 U.mL-1各个剂量组在加S9代谢活化系统于24 h和不加S9代谢活化系统于24 h、48 h培养的CHO细胞染色体畸变率与溶剂对照组比较均无显著差异(P>0.05)。小鼠骨髓微核试验显示425、850、1700 U.kg-1各个剂量组对ICR小鼠的微核诱发率与溶剂对照组比较均无显著差异(P>0.05)。结论聚乙二醇修饰降纤酶对鼠伤寒沙门菌无致突变性,对哺乳动物培养细胞的染色体无致畸变作用,对ICR小鼠无诱发骨髓嗜多染红细胞微核的效应。表明聚乙二醇修饰降纤酶在本实验条件下无遗传毒性。
Objective To detect the genotoxicity of polyethylene glycol modified defibrase. Methods The genotoxicity of polyethylene glycol-modified defibrase was detected by the Salmonella typhimurium mutation test (Ames test), in vitro CHO cell chromosome aberration test and mouse bone marrow micronucleus test. Results The results of Ames test showed that for all dose groups of 100, 20, 4, 0.8 and 0.16 U per dish, histidine-deficient Salmonella typhimurium TA97, TA98, TA100, TA102 and TA1535 The number of induced colonies returned were similar to the number of mutant colonies in the solvent control. Chromosome aberration test of CHO cells cultured in vitro showed that the chromosomal aberrations of CHO cells incubated with S9 metabolic activation system at 24 h and without metabolic activation system of S9 at 24 h and 48 h were observed in 2.5, 5.0 and 10.0 U.mL-1 dose groups, respectively There was no significant difference between the two groups (P> 0.05). Micronucleus test in mice bone marrow showed that there was no significant difference (P> 0.05) between the micronucleus induction rates of ICR mice in 425,850,1700 U.kg-1 dose groups and the solvent control group. CONCLUSION: Polyethylene glycol modified defibrase has no mutagenicity on Salmonella typhimurium and no deleterious effect on the chromosomes of mammalian cultured cells, but does not induce micronuclei in ICR mice. Polyethylene glycol modified defibrase showed no genotoxicity under the experimental conditions.