马兜铃酸致DNA损伤的体外研究  

Study on DNA damage induced by aristolochic acid in vitro

作　　者：李海山[1] 陈新志[1] 仲来福[1] 

机构地区：[1]大连医科大学毒理研究室,辽宁大连116027

出　　处：《毒理学杂志》2005年第4期290-292,共3页Journal of Toxicology

摘　　要：目的研究马兜铃酸(AA)体外致DNA损伤作用。方法采用噻唑蓝比色法比较AA对人胚肾293细胞与转染核苷酸切除修复基因的ERCC1-XPF-293细胞毒性差异;采用单细胞凝胶电泳试验研究AA致293细胞DNA单链断裂作用;以EB荧光法研究AA致牛胸腺DNA交联作用及其代谢活化。结果AA对人胚肾293细胞及ERCC1-XPF-293细胞的半数抑制浓度分别为480.1和661.8μmol/L(P<0.05);AA在60μmol/L即具有致DNA单链断裂作用;加大鼠肝S9条件下AA致牛胸腺DNA交联,同时加入CYP1A抑制剂α-萘黄酮降低DNA交联率。结论AA所致DNA损伤作用是其细胞毒性的重要机制之一。Objective To study the DNA damage induced by aristolochic acid （AA） in vitro. Methods In cultured human embryonic kidney cell lines 293 and ERCC1-XPF-293 transfected with nucleotide excision repair genes, cytotoxicity difference between them induced by AA with methyl thiazolyl tetrazolium（MTY） test was performed. With single cell gel electrophoresis assay the DNA single strand breaks induced by AA in 293 cells were observed. To probe the DNA cross-links induced by AA and its metabolic activation in calf thymus DNA, EB fluorescence assay was used. Results There was significant difference in ICs0 values between AA treated 293 cells and ERCC1-XPF-293 ceils （480.1 and 661.8μmool/L, respectively, P 〈 0.05 ）. AA above 60 μmol/L induced DNA single strand breaks. The DNA cross-links were observed when Sg-mix were added, while which could be decreased by added α-naphthoflavone, an inhibitor of CYP1A. Conclusion DNA damage induced by AA plays an important role in its cytotoxicity.

关 键 词：马兜铃酸 DNA损伤 体外试验 

分 类 号：R99[医药卫生—毒理学]