【摘要】 目的比较过氧亚硝酸阴离子(ONOO-)对正常人胚肝细胞株L-02和肝母细胞瘤细胞株HepG2 DNA损伤和细胞毒性差异,探索ONOO-在肝肿瘤发生中的作用及可能标志物。方法0.01,0.05,0.1 mmol/L ONOO-作用细胞后,检测ONOO-对2株肝细胞的细胞生存率,超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化氢酶(CAT)、丙二醛(MDA)含量变化,DNA损伤,生长抑制DNA损伤基因(GADD)表达的影响差异。结果ONOO-使2种肝细胞的生存率下降、SOD含量降低(P<0.05)和CAT、GSH的显著变化,显著升高MDA的含量;DNA损伤程度和GADD45、GADD153基因表达水平在2株肝细胞均随着剂量的增加显著升高。2种肝细胞相比,各浓度组L-02细胞损伤程度大于HepG2细胞,但只有GADD基因表达水平差异有统计学意义(P<0.05)。结论ONOO-对正常肝细胞和肝癌细胞均显示细胞毒性作用,引起DNA损伤,诱导GADD表达。GADD基因表达水平在不同肝细胞中差异有统计学意义,可能是ONOO-细胞损伤效应的标志物。更多还原

【Abstract】 Objective To compare the DNA damages and cytotoxicit effect of peroxynitrite(ONOO~-)to human embryo liver L-02 cells and human hepatic tumor HepG2 cells. Methods Two liver cells were exposed to different concentration peroxynitrite(0.01,0.05,0.1mmol/L).Survival rate,level of superoxide dismutase(SOD),glutamylcysteinylglycine(GSH),catalase(CAT),Malonyldiadehyde(MDA),DNA damage and the expression level of Growth arrest and DNA damage-inducible genes(GADD)were measured. Results After exposed to peroxynitrite,L-02 and HepG2 cells survival rate decreased from 87.55%,90.34% to 19.21%,21.59% varying concentration ranging 0.01mmol/L to 0.2mmol/L,respectively.0.01mmol/L to 0.2mmol/L,respectively.Peroxynitrite caused GSH,CAT level significantly change,decreased SOD level and increased MED level in L-02 and HepG2 cells(P<0.05).DNA damage and GADD expression level increased as peroxynitrite concentration increased in both two cell lines(P<0.05).All these damages were more serious in L-02 in every concentration level than that of HepG2,but only the expression level of GADD were significant difference between L-02 and HepG2 cells. Conclusion Peroxynitrite had cytotoxicity effect and significant difference was observed in two cells.GADD expression level maybe one of the biomarkers of NONN~-damage effects.更多还原