CAJ | 학술논문

目的探讨hOGG1基因低表达对氢醌(HQ)的细胞毒性及遗传毒性的影响.方法 0、5、10、20、40、80μmol/L浓度的(HQ)染毒A549细胞和hOGG1基因低表达的A549-R细胞,噻唑蓝比色法检测2种细胞存活率,荧光法测定2种细胞内活性氧(ROS)含量,微核试验分析2种细胞染色体损伤,彗星试验观察细胞的DNA损伤和修复.结果随着HQ染毒浓度的增加,2种细胞的存活率均下降,A549-R细胞和A549细胞IC50分别为160.49和228.42 μmol/L,且差异有统计学意义(P＜0.05).0、5、10、20、40、80 μmol/L HQ染毒组A549-R细胞ROS含量、微核率均明显高于A549细胞,差异有统计学意义(P＜0.05);各浓度HQ染毒组A549-R细胞拖尾率和Olive尾距(OTM)值均明显大于A549细胞,并有剂量-反应关系,差异有统计学意义(P＜0.05).hOGG1基因低表达的A549-R细胞比A549细胞对HQ引起的DNA损伤修复更慢,修复2.0 h后才出现拖尾率和OTM值的明显降低,3.0 h后仍未完全修复.结论氧化损伤可能是HQ毒作用的机制之一,hOGG1基因低表达可增加A549-R细胞对HQ的敏感性.
목적 탐토hOGG1기인저표체대경곤(HQ)적세포독성급유전독성적영향.방법 0、5、10、20、40、80μmol/L농도적(HQ)염독A549세포화hOGG1기인저표체적A549-R세포,새서람비색법검측2충세포존활솔,형광법측정2충세포내활성양(ROS)함량,미핵시험분석2충세포염색체손상,혜성시험관찰세포적DNA손상화수복.결과 수착HQ염독농도적증가,2충세포적존활솔균하강,A549-R세포화A549세포IC50분별위160.49화228.42 μmol/L,차차이유통계학의의(P＜0.05).0、5、10、20、40、80 μmol/L HQ염독조A549-R세포ROS함량、미핵솔균명현고우A549세포,차이유통계학의의(P＜0.05);각농도HQ염독조A549-R세포타미솔화Olive미거(OTM)치균명현대우A549세포,병유제량-반응관계,차이유통계학의의(P＜0.05).hOGG1기인저표체적A549-R세포비A549세포대HQ인기적DNA손상수복경만,수복2.0 h후재출현타미솔화OTM치적명현강저,3.0 h후잉미완전수복.결론 양화손상가능시HQ독작용적궤제지일,hOGG1기인저표체가증가A549-R세포대HQ적민감성.
Objective To explore the effects of down-regulated hOGG1 gene expression on cytotoxicity and genotoxicity of hydroquinone.Methods A549 cells and A549-R cells with down-regulated hOGG1 gene were treated with different concentrations of hydroquinone (0,5,10,20,40 and 80 μmol/L).The cellular sensitivity and contents of ROS were measured by MTT assay and fluorescence method,respectively.The chromosome damage was measured by micronucleus test.The DNA damage and repair were examined using comet assay in both cells.Results The cell viability decreased with increasing concentration of hydroquinone.The IC50 of hydroquinone was 160.49 and 228.42 μmol/L in hOGG1 deficient A549-R cell and in A549 cell respectively (P＜0.05).When the dose of hydroquinone reached 5 μmol/L and above,the contents of ROS and the rate of micronucleated ceils in A549-R cells were significantly higher than in A549(P＜0.05 ) cells.At the same time,the comet rate and OTM in A549-R cells were significantly higher compared with A549 cells at 5 μmol/L and above in a dose-response way(P＜0.05 ).Furthermore,in DNA repair assay,A549-R cells with down-regulated hOGG1 gene were more difficult to repair than A549 cells.In A549-R cells,the comet rate and OTM reduced significantly until after 2 h repair time and even after 3 h the DNA damage was not repaired completely.Conclusion Oxidative damage may be one of the toxicological mechanisms of hydroquinone,and hOGG1 deficiency could increase sensitivity of A549- R cells to hydroquinone.