聚乙二醇修饰降纤酶的遗传毒性评价

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。

Evaluation of genetic toxicity of defibrase modified with polyethylene glycol

ATM To investigate the genotoxicity of defibrase modified with polyethylene glycol.METHODS Salmonella typhimurium reverse mutation test(also known as Ames test),in vitro CHO cells chromosome aberration test and mouse bone marrow micronucleus test were used to investigate the genotoxicity of defibrase modified with polyethylene glycol.RESULTS The results of Ames test showed that no change in mean number of revertants per plate in TA97,TA98,TA100,TA102 and TA1535 strains were observed with or without metabolic activation S9 at the dosage of 100,20,4,0.8 and 0.16 U per plate compared to the solvent control.The results in vitro of CHO cell chromosome aberration test indicated that doses of 2.5,5.0 and 10.0 U·mL-1 had no statistical difference(P > 0.05)compared with solvent control in the aberration rates of CHO cells cultured for 24 h with exposure in the metabolic activation S9,or cultured for 24 h and 48 h with or without exposure in the metabolic activation S9(P > 0.05).In the mouse bone marrow micronucleus test,doses of 425,850,1700 U·kg-1 did not increase the number of micronuclei in ICR mice(P > 0.05).CONCLUSION Defibrase modified with polyethylene glycol were not genotoxic under the conditions of the Salmonella typhimurium reverse mutation test,in vitro CHO cells chromosome aberration test or mouse bone marrow micronucleus test.It showed that defibrase modified with polyethylene glycol had no genotoxicity under the conditions of the experiment.