藏茵陈总萜酮的致突变及抗突变作用

The safety and antimutagenicity of total terpene ketones fromSwertia mussotii

目的：研究藏茵陈总萜酮的致突变及抗突变作用。方法：致突变实验采用Ames实验及小鼠体内微核实验。Ames实验采用常规掺入法；微核实验采用连续灌胃给药10 d的骨髓嗜多染红细胞微核计数法。抗突变实验采用体内、体外两种方法，体外法选用TA100及TA102菌株与环磷酰胺（每皿200μg）和丝裂霉素C（每皿2 g）共孵育30 min后，分别给予藏茵陈总萜酮每皿156、312、μ625、1250及2500μg，检测其对阳性剂诱发的已突变菌落的保护作用；体内实验采用藏茵陈总萜酮25、50及100 mg/kg小鼠连续灌胃给药10 d后，给予40 mg/kg环磷酰胺或2 mg/kg丝裂霉素C，计算微核率，检测其对未发生突变的骨髓细胞的保护作用。结果：致突变实验中，藏茵陈总萜酮在每皿〈2500μg剂量下，未诱发Ames实验各菌株回变菌落数增加；在每皿〈40 mg/kg剂量下，未诱发骨髓嗜多染红细胞微核率增高。抗突变实验中，藏茵陈总萜酮在每皿625-2500μg范围内，可使阳性致突变剂环磷酰胺和丝裂霉素C所诱发的高回变菌落数出现明显降低；藏茵陈总萜酮在50-100 mg/kg剂量范围，可使阳性剂环磷酰胺或丝裂霉素C所诱发的高微核率出现明显降低。结论：本实验条件下，藏茵陈总萜酮未表现出诱导基因突变和染色体畸变作用，且有显著的抗突变作用。

OBJECTIVE：To study the mutagenic and anti-mutagenic activities of total terpene ketones from Swertia mussotii （TTKS） at different doses. METHODS：Mutagenic experiments：conventional Ames test and micronucleus test were selected. Ames experiment was used with the incorporation method. Micronucleus test was conducted in mice which were treated orally once a day for 10 days consecutively. Anti-mutagenic experiments：methods in vitro,pre-incubated the TA100 and TA102 strains with CP （200 μg/plate） or MMC （2 μg/plate） for 30 minutes,then mixed the above materials with TTKS （ 156,312,625,1 250 and 2 500 μg/plate ）,so as to detect the protective effects of TTKS on mutational colonies induced by positive agent. Mice were exposed to CP （40 mg/kg） or MMC （2 mg/kg） after continuous irrigation of TTKS （25, 50 and 100 mg/kg ） for 10 days,the micronucleus rate was calculated in order to detect the protective effects of TTKS on non-mutation bone marrow cells. RESULTS：In mutagenic test,TTKS at a dose lower than 2 000 μg/plate induced no obvious increase in mutagenicity of the four strains. TTKS at a dose lower than 40 mg/kg did not increase the micronucleus frequencies of polychromatic erythrocytes. In anti-mutagenic test,comparing with the positive groups of CP and MMC,TTKS at 625-2 500 μg/plate could decrease the colony numbers in T100 and T102 strains. TTKS at 50-100 mg/kg could significantly reduce the rate of micronucleus of polychromatic erythrocytes in mice bone marrow induced by CP and MMC as compared with the positive control. CONCLUSION：Under these experimental conditions,TTKS showed no effect of mutagenesis and could confer significant anti-mutagenic protection.