DNA修复抑制状态下苯并(a)芘对人胚肺成纤维细胞的DNA损伤作用  

Effect of Benzo (a) pyrene on DNA of Human Embryonic Fibroblast under Inhibition of DNA Repair

作　　者：徐永俊[1] 白雪涛[1] 张宏伟[1] 

机构地区：[1]中国疾病预防控制中心环境与健康相关产品安全所,北京100021

出　　处：《环境与健康杂志》2008年第6期472-474,共3页Journal of Environment and Health

基　　金：国家重点基础发展研究计划("973"计划)项目(2002CB512906)

摘　　要：目的研究DNA修复抑制状态下苯并(a)芘[B(a)P]对人胚肺成纤维细胞(HELF)的DNA损伤情况,探讨DNA修复机制在外源性化学致癌物诱导真核细胞DNA损伤中的作用。方法代谢活化条件下,以阿糖胞苷(ara-C,0、100μmol/L)与B(a)P(0、10、20、50μmol/L)按2×4联合染毒2h,通过彗星试验观察不同染毒条件下HELF细胞的DNA损伤情况。同时设阴性对照组(0.1%DMSO)和阳性对照组(10μmol/LK2CrO7)。结果与阴性对照组比较,B(a)P各剂量组的HELF的拖尾率、Olive尾矩随剂量增加而显著升高,差异有统计学意义(P<0.01)。100μmol/Lara-C单独染毒组与阴性对照组比较,拖尾率、Olive尾矩升高,差异有统计学意义(P<0.05,P<0.01)。B(a)P+ara-C组与相应剂量的B(a)P组比较,其拖尾率、Olive尾矩升高,差异有统计学意义(P<0.01)。析因分析表明,ara-C与B(a)P诱导HELF的DNA损伤存在交互作用(F=3.219,P=0.024)。ara-C可增强B(a)P对HELF的DNA损伤作用。结论DNA修复抑制在外源性化学致癌物诱导真核细胞DNA损伤中存在重要作用。Objective To study the effect of benzo（a） pyrene on DNA of human embryonic fibroblast under inhibition of DNA repair,and to explore the mechanism of DNA repair involved in the DNA damage induced by xenobiotic chemical carcinogens. Methods DNA damage of human embryonic lung fibroblast （HELF） induced by benzo（a） pyrene was observed when DNA repair was inhibited by treating HELF with arabinosylcytosin（ara-C） to inhibit the activity of polymerase δ/ε in the cells. With S9 mixture added as metabolic activation system in vitro,HELF was treated for 2 hours with ara-C at the doses of 0 and 100 μmol/L combined with-C at the doses of 0,10,20,50 μmol/L by the 2×4 factor-factorial analysis.Comet assay was used to assess the DNA damage. Results Compared with the control group,the comet rate and Oliver tail moment of groups treated by B（a）P increased significantly （P〈0.01）,when the dosage increased.The comet rate and Oliver tail moment of the group treated by 100 μmmol/L ara-C alone also increased significantly（P〈0.05,P〈0.01）. Factor-factorial analysis showed that there was an interaction between DNA damage in HELF induced by B（a）P and that induced by ara-C. Conclusion Inhibition of DNA repair may play an important role in the carcinogenesis of xenobiotics.

关 键 词：DNA损伤 核苷酸切除修复 苯并(A)芘 

分 类 号：R994.6[医药卫生—毒理学]