托品酸的致突变机制研究

Study on Mutagenicity Mechanism of Tropic Acid

目的:研究托品酸的致突变机制。方法:采用鼠伤寒沙门氏菌回复突变试验,设5 000、2 500、1 250、625μg/皿4个剂量托品酸组、自发回变组、溶剂对照组和阳性对照[非代谢活化条件下:对二甲基氨基苯重氮磺酸钠(Dexon)50μg/皿、注射用丝裂霉素(MMC)0.5μg/皿;代谢活化条件下:2-氨基芴(2-AF)20μg/皿]组,每组6皿,各组在加和不加代谢活化系统S9的条件下,计数组不同致突变类型的氨酸营养缺陷型鼠伤寒沙门氏菌TA97、TA98、TA100、TA102的回变菌落数。结果:与溶剂对照组和自发回变组比较,非活化条件下2 500、5 000μg/皿托品酸组和Dexon阳性对照组TA97、TA98、TA100菌株的回变菌落数均明显增加(P<0.01),MMC阳性对照组TA102菌株的回变菌落数明显增加(P<0.01);活化条件下2 500、5 000μg/皿托品酸组TA98菌株的回变菌落数明显增加(P<0.01),2-AF阳性对照组TA97、TA98、TA100、TA102菌株的回变菌落数均明显增加(P<0.01),其余条件的回变菌落数差异无统计学意义。结论:托品酸的致突变作用机制为诱导组氨酸靶基因中鸟嘌呤-胞嘧啶位点碱基置换和移码突变,活化条件的存在会使其诱变性减弱。

OBJECTIVE： To study the mutagenicity mechanism of tropic acid. METHODS： In Salmonella typhimurium reverse assay, 4 doses of tropic acid groups （5 000, 2 500, 1 250 and 625 lag/vessel）, natural reverse group, solvent control group and positive control group [under non-metabolism activation condition： sodium p（dimethylamino）benzenediazo sulfonate （Dexon） 50 lag/vessel, Mitomycin for injection （MMC） 0.5 lag/vessel; under metabolism activation condition： 2-anlinofluorene （2-AF） 20 μg/ vessel] were set up with 6 vessels in each group. The number of revertant colony of different mutation types of histidine auxotroph Salmonella （yphimurium TA97, TA98. TA100 and TA102 were counted under metabolism activation condition or without metabo- lism activation condition. RESULTS ： Compared with solvent control group and spontaneous revertant group, the number of rever- tant colony of TA97, TA98 and TA100 increased significantly in 2 500 μg/vessel and 5 000 lag/vessel tropic acid groups and Dexon positive control group （P〈0.01）, and the number of revertant colony of TA102 increased significantly in MMC positive control group （P〈0.01） without metabolism activation. Under metabolism activation condition, the number of revertant colony of TA98 in- creased significantly in 2 500 μg/vessel and 5 000μg/vessel tropic acid groups （P〈0.01）; the number of revertant colony of TA97, TA98, TA100 and TAI02 increased significantly in 2-AF positive control group （P〈0.01）. There was no statistical significance in the number of revertant colony under other conditions. CONCLUSIONS： The tropic acid could induce base substitution and frame- shift mutation and the activation system in vitro could reduce the mutagenicity.