The role of nickel and nickel-mediated reactive oxygen species in the mechanism of nickel carcinogenesis.
The role of nickel and nickel-mediated reactive oxygen species in the mechanism of nickel carcinogenesis.
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DOI：
10.1289/ehp.94102s3281
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发表时间：
1994-09
影响因子：
10.4
通讯作者：
Costa M
中科院分区：
文献类型：
--
作者：
Huang X;Zhuang Z;Frenkel K;Klein CB;Costa M
越来越多的证据表明，活性氧物种(ROS)与金属致癌有关。培养的中国仓鼠卵巢(CHO)细胞暴露于几种镍化合物，即NiS、Ni3S2、NiO(黑色和绿色)和NiCl2，可增加2‘，7-二氯荧光素氧化成荧光2’，7-二氯荧光素(DCF)，提示镍化合物增加了CHO细胞中氧化剂的浓度。在胞外介质中加入外源过氧化氢酶可使这种荧光减弱，表明过氧化氢是该体系中形成的氧化剂之一。硫代巴比妥酸反应后的荧光测量表明，镍化合物也会引起脂质过氧化，其强度依次为NiS、Ni3S2>；黑色NiO>；绿色NiO>；NiCl2。这些结果表明，在完整的细胞中，也可能通过镍的作用产生脂质过氧化氢。氯化镁是镍诱导的DNA链断裂和细胞转化的拮抗剂，对镍诱导的CHO细胞DCF荧光的形成没有影响。这些结果表明，镍是完整哺乳动物细胞中ROS的活性诱导剂，镍致癌的分子机制可能涉及镍介导的ROS的多个步骤。
Increasing evidence demonstrates the reactive oxygen species (ROS) are implicated in metal carcinogenesis. Exposure of cultured Chinese hamster ovary (CHO) cells to several nickel compounds, i.e. NiS, Ni3S2, NiO (black and green), and NiCl2 has been shown to increase oxidation of 2',7-dichlorofluorescein to the fluorescent 2',7-dichlorofluorescein (DCF), suggesting that nickel compounds increased the concentration of oxidants in CHO cells. This fluorescence can be attenuated by addition of exogenous catalase to the extracellular media, indicating that H2O2 is one of the formed oxidants in this system. Fluorimetric measurements of chromogens following thiobarbituric acid reaction showed that nickel compounds also induce lipid peroxidation with a decreasing potency NiS, Ni3S2 > black NiO > green NiO > NiCl2. These results suggest that lipid hydroperoxides may also be produced through the action of nickel in intact cells. MgCl2, an antagonist of Ni-induced DNA strand breaks and cell transformation, has no effect on the formation of DCF fluorescence induced in CHO cells by nickel. The results suggest that nickel is an active inducer of ROS in intact mammalian cells and that the molecular mechanism of nickel carcinogenesis may involve multiple steps of nickel-mediated ROS.