癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (5): 398-402.doi: 10.3969/j.issn.1004-616x.2016.05.013

• 检测研究 • 上一篇    下一篇

应用Ames波动试验比较4种马兜铃酸组分的致突变作用

曹易懿1, 刘倩2, 奚晶1, 马雷雷1, 刘晓健3, 栾洋1   

  1. 1. 上海交通大学医学院虹桥国际医学研究院/公共卫生学院, 上海 200025;
    2. 上海诗丹德生物技术有限公司, 上海 201203;
    3. 复旦大学附属肿瘤医院肿瘤内科, 复旦大学上海医学院肿瘤学系, 上海 200032
  • 收稿日期:2016-01-06 修回日期:2016-07-05 出版日期:2016-09-30 发布日期:2016-09-30
  • 通讯作者: 栾洋,E-mail:yluan@sjtu.edu.cn;刘晓健,E-mail:lxj068@hotmail.com E-mail:yluan@sjtu.edu.cn;lxj068@hotmail.com
  • 作者简介:曹易懿,E-mail:yycao@shsmu.edu.cn

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

CAO Yiyi1, LIU Qian2, XI Jing1, MA Leilei1, LIU Xiaojian3, LUAN Yang1   

  1. 1. Hongqiao International Institute of Medicine, Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025;
    2. Shanghai Nature Standard R & D and Biotech Co. Ltd., Shanghai 201203;
    3. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Received:2016-01-06 Revised:2016-07-05 Online:2016-09-30 Published:2016-09-30

摘要: 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。

关键词: 马兜铃酸, Ames波动试验, 遗传毒性, 致突变

Abstract: 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. METHODS: 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 revertant wells of AA-I and AA-Ⅱ were significantly increased in tester strains 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.

Key words: aristolochic acid, Ames fluctuation test, genotoxicity, mutagenicity

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