草酸铂对CHO细胞系野生型AA8和突变型UV20的DNA损伤作用  

Study on DNA damage caused by oxaliplatin in CHO cell line AA8 and UV20

作　　者：逯晓波[1] 蔡原[1] 刘秋芳[1] 安春丽[2] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理教研室,辽宁沈阳110001 [2]中国医科大学基础医学院病原生物学教研室

出　　处：《毒理学杂志》2008年第3期188-190,191,共4页Journal of Toxicology

基　　金：国家自然科学基金资助项目(30471475)

摘　　要：目的探讨交叉互补集团1基因(ERCC1)蛋白在草酸铂毒性作用的影响,找寻草酸铂药物抵抗性的关键因子。方法中国仓鼠卵巢细胞系野生型AA8以及ERCC1表达缺失型UV20可以作为细胞对照模型。SRB细胞抑制率实验、改良彗星实验、Rad51免疫荧光实验评价草酸铂染毒后不同时点的DNA损伤程度。结果AA8和UV20对草酸铂的敏感性不同,IC50相差近16倍。改良彗星实验和Rad51免疫荧光实验同时表明,AA8与UV20相比,具有修复草酸铂所致DNA损伤能力。结论ERCC1蛋白具有重要的核酸内切酶功能,对于修复草酸铂所致DACH-Pt-DNA加合物具有重要意义。Objective To elucidate the effect of ERCC1 on Oxaliplatin cytotoxicity and finding the key element related to Oxaliplatin anti-tumor resistance.Methods China Hamster Ovary（CHO） cell line including wildtype AA8 and ERCC1 defective mutant UV20,as a cell contrast model,DNA damage levels at different time points after Oxaliplatin treatment were evaluated by SRB cell inhibition assay,modified comet assay,Rad51 immuno-fluorescence test.Results UV20 comparing with AA8,IC50 of Oxaplatin decreased more than 16 times,and more sensitive to Oxaplatin.The DNA damage caused by Oxaliplatin repaired by AA8 but not by UV20 through modified comet assay and Rad51 test.Conclusion ERCC1 is an important endonuclease relating to excising DACH-Pt-DNA adduct cause by Oxaliplatin.

关 键 词：交叉互补集团1基因 草酸铂 DNA损伤与修复 细胞模型 

分 类 号：R994[医药卫生—毒理学]