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镍和镉对人外周血淋巴细胞的DNA损伤作用 |
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蔡颖 庄志雄
【摘要】 目的 了解不同类型DNA损伤在镍、镉遗传毒理中的不同意义。方法 分别用NiCl2和CdCl2对人外周血淋巴细胞进行体外染毒，再用单细胞凝胶电泳法，测定其DNA单链、双链断裂和DNA-蛋白质交联水平，同时用［3H］-NAD参入法测定了这些细胞的聚(腺苷二磷酸-核糖)聚合酶(PARP)活性。结果 尽管在两种金属处理过的细胞中DNA单链、双链断裂和DNA-蛋白质交联水平与对照相比均有明显增高，但只有0.10～10.00 μmol/L的NiCl2和0.16～20.00 μmol/L的CdCl2诱导的DNA双链断裂呈剂量反应关系。两种金属在低浓度时(NiCl2 0.10～0.40 μmol/L，CdCl2 0.16 μmol/L)还能通过诱导DNA断裂而激活PARP, 高浓度时(NiCl2 2.00～10.00 μmol/L，CdCl2 0.80～20.00 μmol/L)反而不激活该酶。结论 DNA双链断裂的形成和PARP激活的受阻可能在镍和镉的致癌和致突变机制中起着重要的作用。
【关键词】 镍 镉 DNA损伤 NAD+ADP核糖转移酶
DNA Damage in Human Peripheral Blood Lymphocyte Caused by Nickel and Cadmium CAI Ying*, ZHUANG Zhixiong. *Laboratory Center, Shantou Bureau of Health Quarantine Service, Guangdong 515031
【Abstract】 Objective To understand the different implication of various forms of DNA damage in genotoxicity of nickel and cadmium. Methods Human peripheral lymphocyte was exposed to nickel chloride and cadmium chloride in vitro. Levels of DNA single-and double-strand breaks and DNA-protein crosslinks in human peripheral lymphocyte were determined with single cell gel electrophoresis (SCGE). Activity of poly (ADP-ribose) polymerase (PARP) was determined by ［3H］-NAD incorporating method. Results Levels of DNA single-and double-strand breaks and DNA-protein crosslinks in human peripheral lymphocyte treated with nickel and cadmium were significantly higher than those untreated, but dose-response relationship only showed in those treated with 0.10～10.00 μmol/L of nickel chloride and 0.16～20.00 μmol/L of cadmium. Low levels of the two kinds of metal (0.10～0.40 μmol/L of nickel and 0.16 μmol/L of cadmium) could induce the cleavage of DNA and activate PARP, and high levels of the two kinds of metal (2.00～10.00 μmol/L of nickel and 0.80～20.00 μmol/L of cadmium) could not induce the enzyme cleavage of DNA. Conclusion Formation and cleavage of DNA double strand and blockage of activation of PARP can play an importa[1] [2] 下一页
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