镍致DNA链断裂及对聚腺苷二磷酸核糖聚酶活性的影响

Study in vitro on the activity of poly(ADP-ribose)polymerase(PARP)and DNA strand breakage induced by nickel

目的 探讨镍所致DNA链断裂及其所诱导的聚腺苷二磷酸核糖聚酶 (PARP)之间的关系。方法 培养猴肾Vero细胞 ,分别用 0、12 5、2 5 0、5 0 0、10 0 0 μmol L的醋酸镍染毒 2 5、6和 12h ;苔盼蓝计数法检测细胞存活率 ,单细胞凝胶电泳法检测DNA链断裂 ,3H掺入法检测PARP活性。结果 镍浓度与DNA链断裂程度之间存在剂量 效应和时间 效应关系 ;镍也可诱导PARP活性显著升高 ,但在高浓度和长时间染毒时 ,其活性不再增加。结论 镍所致的DNA链断裂与其诱导的PARP活性之间存在特殊关系 ,这可能与镍的致癌性相关。

Objective To probe into the association between DNA strand breakage induced by nickel and the activity of poly(ADP-Ribose)Polymerase(PARP).Methods Vero cells were contaminated with nickel acetate,which concentration was 0,125,250,500,1 000 μmol/L and duration was 2.5,6 and 12 hours respectively.Cell survival rate,DNA strand breakage(DSB) and activity of PARP were detected with typan blue,single cell gel electrophoresis(SCGE) and 3H labeled method respectively.Results There were dose-effect and dose-time relationships between nickel and DSB.The activity of PARP was significantly increased by induction of nickel,but kept flat while higher concentration or longer duration of contamination.Conclusion There was a special associaton between activity of PARP and DSB induced by nickel,which might be the carcinogenic mechanism of nickel.