草苔虫内酯的遗传毒性评价

目的：检测草苔虫内酯的遗传毒性。方法：采用Ames试验、体外培养中国仓鼠卵巢（chinese hamsterovary，crto）细胞染色体畸变试验和小鼠骨髓微核试验检测草苔虫内酯的遗传毒性。结果：Ames试验显示在每皿100、10、1、0．1g受试剂量下，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氏菌TA97、TA98、TA100、TA102及TAl535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，在3．75、1．88和0．94g／ml 3个剂量组，在加S9条件下培养24h和不加S9培养24、48h的CHO细胞染色体畸变率与溶剂对照组相比差异有统计学意义（P〈0．05）。小鼠骨髓微核试验，在12．5、25、50g／kg3个剂量下对ICR小鼠的微核诱发率呈剂量反应关系，与溶剂对照组相比差异有统计学意义（P〈0．01）。结论：在本实验条件下，草苔虫内酯对鼠伤寒沙门氏菌无致突变性，对哺乳动物培养细胞染色体的致畸变作用为可疑阳性，对ICR／b鼠有诱发骨髓嗜多染红细胞微核的效应，提示草苔虫内酯对人体具有潜在的遗传毒性。

Evaluation of genetic toxicity of bryostatin

OBJECTIVE:To evaluate the genetic toxicity of bryostatin.METHODS:Ames test,chromosomal aberration test of chinese hamster ovary(CHO) cell and micronucleus assay were used to investigate the genetic toxicity of bryostatin.RESULTS:The results of Ames test showed that no change in mean number of revertants per plate in TA97,TA 98,TA 100,TA 102 and TA 1535 strains were observed with or without metabolic activation of S9 at the dosages of 100, 10,1,0.1 g per plate compared to the negative control.The in vitro results of CHO cell chromosomal aberration test indicated that doses of 3.75μg/ml,1.88μg/ml and 0.94μg/ml caused statistically significant difference(P>0.05) compared with negative controlsin the aberration rates of CHO cells cultured for 24 h with metabolic activation of S9,or cultured for 24 h and 48 h without the metabolic activation of S9.In vivo mice marrow micronucleus test showed that bryostatin had the inductive effect of polychromatophilic erythrocyte micronucleus formation under the dosages of 12.5,25 and 50μg/kg. Compared with negative control,the differences of those exposed to treatment were all significant(P<0.01).CONCLUSION: These results indicated that bryostatin did not show genetic toxicity based on the Ames test,but could adversely affect chromosomal aberration and micronucleus formation under our experimental conditions.