应用Ames波动试验比较4种马兜铃酸组分的致突变作用

Comparative evaluation of mutagenicity of four aristolochic acids components using the Ames fluctuation test

目的:比较4种马兜铃酸组分(AA-I、AA-II、AA-III和AA-IV)的致突变作用,初步考察其毒性作用与分子结构之间的关系。方法:应用鼠伤寒沙门氏菌TA98和TA100菌株对马兜铃酸4个组分采用Ames波动试验方法在非代谢活化(-S9)和代谢活化(+S9)条件下进行细菌回复突变试验。结果:试验结果显示,AA-I与AA-II在-S9和+S9条件下对TA98和/或TA100菌株的回复突变孔数与阴性对照组相比明显增加,差异具有统计学意义(P<0.05)。AA-II的回复突变孔数呈剂量依赖性增加,且在多个剂量下回复突变孔数超过基线值的倍数大于AA-I。AA-III和AA-IV对2株菌株的回复突变孔数未见明显增加,但AA-IV在+S9条件下对TA100菌株在各个剂量下的回复突变孔数呈剂量依赖性增加。结论:AA-I和AA-II均显示出较强的致突变作用,且AA-II致突变作用强于AA-I。AA-IV在+S9条件下可能有潜在的致突变作用;AA-III对2株菌株均未见致突变作用。4种马兜铃酸组分的致突变毒性程度不同,认为可能与其化学结构及代谢特征不同有关。

OBJECTIVE： To compare the mutagenicity among four components of aristolochic acid （AA-I,AA- II,AA-III and AA-IV） using the Ames fluctuation test,and to evaluate the relationship between toxicity mechanisms and molecular structures of aristolochic acid. ME T HODS ： Two Salmonella typhimurium tester strains （TA98 and TA100） were employed to perform the Ames fluctuation test in the absence and presence of the S9 exogenous metabolic activation system. RESULTS ：The mean number of rever tant wel ls of AA-I and AA-II were signi f icant ly increased in tester s trains TA98 and/or TA100,with and without S9 （P〈0.05）. AA-II showed a clear dose-response increase and the fold inductions in mean number of revertant wells over the baseline of AA-II and more than AA-I. Both AA-III and AA-IV did not induce significant increase with the two test strains,but AA-IV showed a trend of dose-response increase. CONCLUSION ： AA-I and AA-II were mutagenic with or without metabolic activation＇and the mutagenicity of AA-II was stronger than that of AA-I. AA-IV demonstrated mutagenicity with metabolic activation. AA-III did not show mutagenicity in the two tester strains. The four aristolochic acids exhibited different levels of mutagenicity which might be due to their different structural and metabolic characteristics.