中华放射医学与防护杂志
中華放射醫學與防護雜誌
중화방사의학여방호잡지
Chinese Journal of Radiological Medicine and Protection
2010年
2期
133-137
,共5页
hOGGl基因%放射敏感性%辐射%核酶
hOGGl基因%放射敏感性%輻射%覈酶
hOGGl기인%방사민감성%복사%핵매
hOGGl gene%Radiosensitivity%Radiation%Ribozyme
目的 观察~(60)Co γ射线对核酶诱导的hOGGl基因低表达的人肺腺癌A549细胞的损伤效应,探讨hOGGl低表达在增加肿瘤细胞放疗敏感性中的作用机制.方法 以A549细胞、转染空质粒的A549-P细胞和转染hOGGl特异性锤头状核酶真核表达载体pcDNA3.1(+)-RZ的A549-R细胞为研究对象,测定射线照射后3种细胞活性氧含量、细胞存活率、细胞染色体损伤及DNA损伤和修复的差异.结果 A549、A549-P和A549-R 3种细胞的存活率随~(60)Co γ射线照射剂量的增加而下降,存在较好的剂量-反应关系(r=-0.984、-0.978、-0.975,P<0.05).A549-R细胞的IC_(50)(9.37±0.24)显著低于A549细胞(12.98±0.44),差异有统计学意义(t=-12.48,P<0.05).~(60)Co γ射线照射下细胞活性氧含量、微核形成率及DNA损伤均增加,在相同剂量下,A549-R细胞中活性氧含量和微核形成率均高于A549和A549-P细胞.此外,在相同照射剂量下,hOGGl缺陷的A549-R细胞的DNA损伤较A549和A549-P细胞严重,且损伤后更加不易修复.结论 ~(60)co γ射线可以诱导A549、A549-P和A549-R 3种试验细胞的活性氧增加,从而导致DNA和染色体损伤,最终使细胞存活率降低.且以hOGGl低表达的A549-R细胞更为明显,提示hOGGl基因的低表达可能增加肿瘤细胞对射线的敏感性.
目的 觀察~(60)Co γ射線對覈酶誘導的hOGGl基因低錶達的人肺腺癌A549細胞的損傷效應,探討hOGGl低錶達在增加腫瘤細胞放療敏感性中的作用機製.方法 以A549細胞、轉染空質粒的A549-P細胞和轉染hOGGl特異性錘頭狀覈酶真覈錶達載體pcDNA3.1(+)-RZ的A549-R細胞為研究對象,測定射線照射後3種細胞活性氧含量、細胞存活率、細胞染色體損傷及DNA損傷和脩複的差異.結果 A549、A549-P和A549-R 3種細胞的存活率隨~(60)Co γ射線照射劑量的增加而下降,存在較好的劑量-反應關繫(r=-0.984、-0.978、-0.975,P<0.05).A549-R細胞的IC_(50)(9.37±0.24)顯著低于A549細胞(12.98±0.44),差異有統計學意義(t=-12.48,P<0.05).~(60)Co γ射線照射下細胞活性氧含量、微覈形成率及DNA損傷均增加,在相同劑量下,A549-R細胞中活性氧含量和微覈形成率均高于A549和A549-P細胞.此外,在相同照射劑量下,hOGGl缺陷的A549-R細胞的DNA損傷較A549和A549-P細胞嚴重,且損傷後更加不易脩複.結論 ~(60)co γ射線可以誘導A549、A549-P和A549-R 3種試驗細胞的活性氧增加,從而導緻DNA和染色體損傷,最終使細胞存活率降低.且以hOGGl低錶達的A549-R細胞更為明顯,提示hOGGl基因的低錶達可能增加腫瘤細胞對射線的敏感性.
목적 관찰~(60)Co γ사선대핵매유도적hOGGl기인저표체적인폐선암A549세포적손상효응,탐토hOGGl저표체재증가종류세포방료민감성중적작용궤제.방법 이A549세포、전염공질립적A549-P세포화전염hOGGl특이성추두상핵매진핵표체재체pcDNA3.1(+)-RZ적A549-R세포위연구대상,측정사선조사후3충세포활성양함량、세포존활솔、세포염색체손상급DNA손상화수복적차이.결과 A549、A549-P화A549-R 3충세포적존활솔수~(60)Co γ사선조사제량적증가이하강,존재교호적제량-반응관계(r=-0.984、-0.978、-0.975,P<0.05).A549-R세포적IC_(50)(9.37±0.24)현저저우A549세포(12.98±0.44),차이유통계학의의(t=-12.48,P<0.05).~(60)Co γ사선조사하세포활성양함량、미핵형성솔급DNA손상균증가,재상동제량하,A549-R세포중활성양함량화미핵형성솔균고우A549화A549-P세포.차외,재상동조사제량하,hOGGl결함적A549-R세포적DNA손상교A549화A549-P세포엄중,차손상후경가불역수복.결론 ~(60)co γ사선가이유도A549、A549-P화A549-R 3충시험세포적활성양증가,종이도치DNA화염색체손상,최종사세포존활솔강저.차이hOGGl저표체적A549-R세포경위명현,제시hOGGl기인적저표체가능증가종류세포대사선적민감성.
Objective To study the mechanism of hOGGl down-regulation mediated by hOGGl ribozyme on increasing the radiosensitivity to tumor cells by observing the damage effects induced by ~(60)Co γ-rays on human lung cancer cell line.Methods Human lung adenocarcinoma A549 cells,A549-P cells transfected with empty pcDNA3.1 plasmid and A549-R cells transfected with pcDNA3.1-RZ plasmid in which hOGGl ribozyme was constructed previously were utilized as a model system.The three kinds of cells were exposed to different doses of~(60)Co γ-rays.The level of cellular reactive oxygen species (ROS),the cell viability,the chromosome damage as well as DNA damage and repair were examined respectively. Results The eell viability decreased significantly among A549,A549-P and A549-R cells after exposure to~(60)Co-γ rays with a dose-response relationship(r=-0.984,-0.978,-0.975,P<0.05),and the IC_(50) in A549-R cells (9.37±0.24) was statistically Iower than that in A549 cells (12.98±0.44,t=-l2.48,P<0.05).The ROS level.the rate of micronucleus formation and DNA damage in all three kinds of cells were enhanced after exposure to~(60)Co γ-rays,in which A549-R cells presented the most remarkable effeet compared with A549 and A549-P cells.Similarly.DNA damage in A549-R cells was also more severe and more difficult to be repaired than that in A549 and A549-P cells at the same dose.Conclusions ~(60)Co γ-rays can induce DNA and chromosome damage in A549 cells through the ROS accumulation,leading to the reduction of the eell viability.However,all effects detected were more remarkable in A549-R cells in which hOGGl was down-regulated mediated by ribozyme,suggesting that the deficiency in hOGGl might increase the radiosensivity in tumor cells.
